Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
September-2025 Volume 32 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2025 Volume 32 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data1.xlsx
    • Supplementary_Data2.xlsx
    • Supplementary_Data3.xlsx
Article Open Access

Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning

  • Authors:
    • Huidi Tang
    • Kang Li
    • Xiaojie Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
    Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 249
    |
    Published online on: July 8, 2025
       https://doi.org/10.3892/mmr.2025.13614
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Diabetic nephropathy (DN) is the main cause of end‑stage renal disease, with epithelial‑mesenchymal transition (EMT) serving a key role in its initiation and progression. Nevertheless, the precise mechanisms involved remain unidentified. The present study aimed to identify the involvement of EMT‑related genes in the advancement of DN. Using the Gene Expression Omnibus database and the dbEMT 2.0 database, EMT‑related differentially expressed genes (DEGs) associated with DN were identified. Key EMT‑related genes were subjected to weighted gene co‑expression network analysis, machine learning and protein‑protein interaction network analyses and validated against validation datasets from GEO database. Receiver operating characteristic analysis was used to assess the diagnostic performance of these hub genes. To delve into their cellular clustering in DN, single‑nucleus RNA sequencing was conducted using the Kidney Integrative Transcriptomics database. Additionally, the CIBERSORT algorithm was used to determine the proportion of immune cell infiltration in DN samples. Reverse transcription‑quantitative PCR (RT‑qPCR) was used to assess the mRNA expression of fibronectin 1 (FN1) in the kidney of mice and patients with DN. After silencing FN1, the expression changes of EMT markers (E‑cadherin and vimentin) were detected by RT‑qPCR. FN1 was upregulated in DN, demonstrating good diagnostic performance according to ROC analysis. FN1 was associated with infiltration of immune cells. RT‑qPCR confirmed the increased expression of FN1 in the kidney of mice with DN and in the renal biopsy samples of patients with DN. After silencing FN1, the expression of E‑cadherin was upregulated, while the expression of vimentin was downregulated, indicating that EMT was inhibited. The present study identified FN1 as a diagnostic marker for DN. FN1 may serve key roles in the initiation and progression of DN by participating in EMT and upregulating various types of immune cells.
View Figures

Figure 1

Identification of DEGs in dataset no.
GSE96804 from the Gene Expression Omnibus database. (A) Volcano
plot of DEGs in dataset GSE96804. (B) Heatmap of DEGs. (C) UMAP
illustrating the different groups. DEG, differentially expressed
gene; DN, diabetic nephropathy; UMAP, uniform manifold
approximation and projection.

Figure 2

Construction of the co-expression
network. (A) β=11 was selected as the soft threshold with the
combined analysis of scale independence and mean connectivity based
on top 25% of genes with the highest variance. (B) Gene hierarchy
tree-clustering diagram. Colors represent different module genes.
(C) Heatmap of the correlation between module genes and phenotypes.
(D) Venn diagram of the module genes from WGCNA, differentially
expressed in GSE96804 and EMT-related genes. EMT,
epithelial-mesenchymal transition; WGCNA, weighted gene
co-expression network analysis.

Figure 3

Screening of potential small molecule
compounds for the treatment of diabetic nephropathy via CMap
database. (A) Top 10 compounds with the most significantly negative
connectivity scores across 9 different cell lines. (B) Chemical
structures of compounds. CMap, connectivity map; pc, principal
component.

Figure 4

Screening hub genes using the STRING
database by intersecting the top genes obtained from degree, MCC
and MNC algorithms. (A) Protein-protein interaction network. Top 10
genes based on (B) degree, (C) MCC and (D) MNC. (E) Venn diagram of
the genes screened from degree, MCC and MNC. MNC, maximum
neighborhood component; MCC, maximal clique centrality.

Figure 5

Potential molecular subtypes of
diabetic nephropathy based on hub genes from dataset no. GSE96804
of the Gene Expression Omnibus. (A) Consensus matrix heatmap when
k=2. (B) Representative CDF curves. (C) Score of consensus
clustering. (D) Principal component analysis plot of the
distribution of two clusters. CDF, cumulative distribution
function; Dim, dimension

Figure 6

Identification of diagnostic markers
using machine learning to conduct validation. (A) Least absolute
shrinkage and selection operator regression algorithm. (B) Support
vector machine recursive feature elimination algorithm. (C)
Expression of diagnostic markers in the GSE47183 and GSE104948
datasets from Gene Expression Omnibus. *P<0.05, **P<0.01. (D)
ROC curve analysis of diagnostic markers in the GSE47183 and
GSE104948 datasets. DN, diabetic neuropathy; AUC, area under the
curve; CI, confidence interval; CV, cross validation; TPR, true
positive rate; FPR, false positive rate.

Figure 7

Gene set enrichment analysis of FN1.
Co-enriched (A) Gene Ontology terms and (B) Kyoto Encyclopedia of
Genes and Genomes pathways.

Figure 8

Single nucleus RNA sequencing from
the Kidney Integrative Transcriptomics database. (A) Annotation of
cluster subtypes. (B) Expression distribution of FN1. (C) Percent
expression of FN1 in cell clusters. PCT, proximal convoluted
tubule; CD, collecting duct; ICA, Type A intercalated cell; PEC,
parietal epithelial cell; PC, principal cell; DCT, distal
convoluted tubule; CT, connecting tubule; LOH, loop of Henle; PODO,
podocyte; ENDO, endothelium; MES, mesangial cell; LEUK, leukocyte;
tSNE, t-distributed stochastic neighbor embedding; FN1, fibronectin
1; CTRL, control.

Figure 9

Immune cell infiltration analysis
based on dataset GSE96804 from the Gene Expression Omnibus
database. (A) Infiltrating immune cells in DN and normal samples.
(B) Spearman's correlation analysis of FN1 and immune cells.
*P<0.05, **P<0.01 and ***P<0.001. DN, diabetic neuropathy;
NK, natural killer; FN1, fibronectin 1; Cor, correlation.

Figure 10

Validation of the expression of FN1
in the kidney of mice with DN and in patients with DN. Relative
expression of FN1 mRNA in (A) kidney of mice (n=6) and (B) human
kidney renal biopsy samples. Relative expression levels of (C) FN1,
(D) E-cadherin and (E) vimentin in HK-2 cells (n=3). Data are
expressed as the mean ± SD. *P<0.05. FN1, fibronectin 1; siRNA,
small interfering RNA; DN, diabetic neuropathy.
View References

1 

Webster AC, Nagler EV, Morton RL and Masson P: Chronic kidney disease. Lancet. 389:1238–1252. 2017. View Article : Google Scholar

2 

Pozo Garcia L, Thomas SS, Rajesh H and Navaneethan SD: Progress in the management of patients with diabetes and chronic kidney disease. Curr Opin Nephrol Hypertens. 31:456–463. 2022. View Article : Google Scholar : PubMed/NCBI

3 

Umanath K and Lewis JB: Update on diabetic nephropathy: Core curriculum 2018. Am J Kidney Dis. 71:884–895. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Flyvbjerg A: The role of the complement system in diabetic nephropathy. Nat Rev Nephrol. 13:311–318. 2017. View Article : Google Scholar

5 

Tung CW, Hsu YC, Shih YH, Chang PJ and Lin CL: Glomerular mesangial cell and podocyte injuries in diabetic nephropathy. Nephrology (Carlton). 23 (Suppl 4):S32–S37. 2018. View Article : Google Scholar

6 

Mandelbrot DA, Reese PP, Garg N, Thomas CP, Rodrigue JR, Schinstock C, Doshi M, Cooper M, Friedewald J, Naik AS, et al: KDOQI US Commentary on the 2017 KDIGO clinical practice guideline on the evaluation and care of living kidney donors. Am J Kidney Dis. 75:299–316. 2020. View Article : Google Scholar : PubMed/NCBI

7 

Radcliffe NJ, Seah JM, Clarke M, MacIsaac RJ, Jerums G and Ekinci EI: Clinical predictive factors in diabetic kidney disease progression. J Diabetes Investig. 8:6–18. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Wang K, Hu J, Luo T, Wang Y, Yang S, Qing H, Cheng Q and Li Q: Effects of Angiotensin-converting enzyme inhibitors and Angiotensin II receptor blockers on All-Cause mortality and renal outcomes in patients with diabetes and albuminuria: A systematic review and Meta-analysis. Kidney Blood Press Res. 43:768–779. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Palmer SC, Tendal B, Mustafa RA, Vandvik PO, Li S, Hao Q, Tunnicliffe D, Ruospo M, Natale P, Saglimbene V, et al: Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: Systematic review and network meta-analysis of randomised controlled trials. BMJ. 372:m45732021. View Article : Google Scholar : PubMed/NCBI

10 

American Diabetes Association. 6. Glycemic Targets, . Standards of medical care in diabetes-2020. Diabetes Care. 43 (Suppl 1):S66–S76. 2020. View Article : Google Scholar : PubMed/NCBI

11 

Taylor SI: GLP-1 receptor agonists: Differentiation within the class. Lancet Diabetes Endocrinol. 6:83–85. 2018. View Article : Google Scholar

12 

Ayodele OE, Alebiosu CO and Salako BL: Diabetic nephropathy-a review of the natural history, burden, risk factors and treatment. J Natl Med Assoc. 96:1445–1454. 2004.

13 

Saito N, Toyoda M, Kondo M, Abe M, Sanechika N, Kimura M, Sawada K and Fukagawa M: Regulation of renin expression by Β1-Integrin in As4.1 juxtaglomerular line cells. Biomedicines. 11:5012023. View Article : Google Scholar : PubMed/NCBI

14 

Writing Group of 2018 Chinese Guidelines for the Management of Hypertension, Chinese Hypertension League, Chinese Society of Cardiology, Chinese Medical Doctor Association Hypertension Committee, Hypertension Branch of China International Exchange, Promotive Association for Medical, Health Care and the Hypertension Branch of Chinese Geriatric Medical Association, . 2018 Chinese guidelines for the management of hypertension. Chin J Cardiovasc Med. 24:24–56. 2019.(In Chinese).

15 

Han H, Chen Y, Yang H, Cheng W, Zhang S, Liu Y, Liu Q, Liu D, Yang G and Li K: Identification and verification of diagnostic biomarkers for glomerular injury in diabetic nephropathy based on machine learning algorithms. Front Endocrinol (Lausanne). 13:8769602022. View Article : Google Scholar : PubMed/NCBI

16 

Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 15:178–1796. 2014. View Article : Google Scholar

17 

Cruz-Solbes AS and Youker K: Epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT): Role and implications in kidney fibrosis. Results Probl Cell Differ. 60:345–372. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Liu R, Mu J, Chen X, Zhang Y, Gao X, Li L, Luo Q, Feng Q, He S and Pu D: miR-126-5p influences epithelial-mesenchymal transition in renal tubular epithelial cells of diabetic nephropathy by targeting Peli2. Anhui Med Pharmaceutical J. 25:1428–1432

19 

Guo HB, Liu YX, Jia JY and Yan TK: miR-451 negatively regulates EMT of the diabetic nephropathy by Akt. Basic Clin Med. 40:469–472. 2020.

20 

Li Y, Zhang Y, Shi H, Liu X, Li Z, Zhang J, Wang X, Wang W and Tong X: CRTC2 activates the epithelial-mesenchymal transition of diabetic kidney disease through the CREB-Smad2/3 pathway. Mol Med. 29:1462023. View Article : Google Scholar : PubMed/NCBI

21 

Jia J, Tan R, Xu L, Wang H, Li J, Su H, Zhong X, Liu P and Wang L: Hederagenin improves renal fibrosis in diabetic nephropathy by regulating Smad3/NOX4/SLC7A11 signaling-mediated tubular cell ferroptosis. Int Immunopharmacol. 135:1123032024. View Article : Google Scholar

22 

Li Y, Hu Q, Li C, Liang K, Xiang Y, Hsiao H, Nguyen TK, Park PK, Egranov SD, Ambati CR, et al: PTEN-induced partial epithelial-mesenchymal transition drives diabetic kidney disease. J Clin Invest. 129:1129–1151. 2019. View Article : Google Scholar

23 

Li X, Miao Y, Li T, Liu X, Xu L, Guo J, Yu X, Sun B, Zhu Y, Ai D and Chen L: Integrin β6 mediates epithelial-mesenchymal transition in diabetic kidney disease. Mol Cell Endocrinol. 572:1119552023. View Article : Google Scholar

24 

Daniels Gatward LF, Kennard MR, Smith LIF and King AJF: The use of mice in diabetes research: The impact of physiological characteristics, choice of model and husbandry practices. Diabet Med. 38:e147112021. View Article : Google Scholar : PubMed/NCBI

25 

Leary S, Underwood W, Anthony R, Cartner S, Grandin T, Greenacre C, Gwaltney-Brant S, McCrackin MA, Meyer R, Miller D, et al: AVMA Guidelines for the Euthanasia of Animals: 2020 edition. Available from:. https://www.avma.org/sites/default/files/2020-02/Guidelines-on-Euthanasia-2020.pdf

26 

Pan Y, Jiang S, Hou Q, Qiu D, Shi J, Wang L, Chen Z, Zhang M, Duan A, Qin W, et al: Dissection of glomerular transcriptional profile in patients with diabetic nephropathy: SRGAP2a protects podocyte structure and function. Diabetes. 67:717–730. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Ju W, Greene CS, Eichinger F, Nair V, Hodgin JB, Bitzer M, Lee YS, Zhu Q, Kehata M, Li M, et al: Defining cell-type specificity at the transcriptional level in human disease. Genome Res. 23:1862–1873. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Grayson PC, Eddy S, Taroni JN, Lightfoot YL, Mariani L, Parikh H, Lindenmeyer MT, Ju W, Greene CS, Godfrey B, et al: Metabolic pathways and immunometabolism in rare kidney diseases. Ann Rheum Dis. 77:1226–1233. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Yang C, Delcher C, Shenkman E and Ranka S: Machine learning approaches for predicting high cost high need patient expenditures in health care. Biomed Eng Online. 17 (Suppl 1):S1312018. View Article : Google Scholar

30 

Zhang J, Yu R, Guo X, Zou Y, Chen S, Zhou K, Chen Y, Li Y, Gao S and Wu Y: Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies. Bioengineered. 12:2214–2227. 2021. View Article : Google Scholar : PubMed/NCBI

31 

Lin X, Li C, Zhang Y, Su B, Fan M and Wei H: Selecting feature subsets based on SVM-RFE and the overlapping ratio with applications in bioinformatics. Molecules. 23:522017. View Article : Google Scholar : PubMed/NCBI

32 

Li K, Tang H, Cao X, Zhang X and Wang X: PTEN: A novel diabetes nephropathy protective gene related to cellular senescence. Int J Mol Sci. 26:30882025. View Article : Google Scholar

33 

Wilson PC, Wu H, Kirita Y, Uchimura K, Ledru N, Rennke HG, Welling PA, Waikar SS and Humphreys BD: The single-cell transcriptomic landscape of early human diabetic nephropathy. Proc Natl Acad Sci USA. 116:19619–19625. 2019. View Article : Google Scholar : PubMed/NCBI

34 

Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M and Alizadeh AA: Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 12:453–457. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

36 

Fu Y, Sun Y, Wang M, Hou Y, Huang W, Zhou D, Wang Z, Yang S, Tang W, Zhen J, et al: Elevation of JAML promotes diabetic kidney disease by modulating podocyte lipid metabolism. Cell Metab. 32:1052–1062.e8. 2020. View Article : Google Scholar : PubMed/NCBI

37 

Li Y, Duan Y, Chu Q, Lv H, Li J, Guo X, Gao Y, Liu M, Tang W, Hu H, et al: G-protein coupled receptor GPR124 protects against podocyte senescence and injury in diabetic kidney disease. Kidney Int. 107:652–665. 2025. View Article : Google Scholar

38 

Xu Z, Jia K, Wang H, Gao F, Zhao S, Li F and Hao J: METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial-mesenchymal transition of renal tubular cells in diabetic kidney disease. Cell Death Dis. 12:322021. View Article : Google Scholar : PubMed/NCBI

39 

Singh M, Yelle N, Venugopal C and Singh SK: EMT: Mechanisms and therapeutic implications. Pharmacol Ther. 182:80–94. 2018. View Article : Google Scholar : PubMed/NCBI

40 

Aiello NM and Kang Y: Context-dependent EMT programs in cancer metastasis. J Exp Med. 216:1016–1026. 2019. View Article : Google Scholar : PubMed/NCBI

41 

Alicic RZ, Rooney MT and Tuttle KR: Diabetic kidney disease: Challenges, progress, and possibilities. Clin J Am Soc Nephrol. 12:2032–2045. 2017. View Article : Google Scholar

42 

Li A, Peng R, Sun Y, Liu H, Peng H and Zhang Z: LincRNA 1700020I14Rik alleviates cell proliferation and fibrosis in diabetic nephropathy via miR-34a-5p/Sirt1/HIF-1α signaling. Cell Death Dis. 9:4612018. View Article : Google Scholar : PubMed/NCBI

43 

Zhang LH, Liu JY and Wang RX: Research progress on the regulatory mechanism of epithelial mesenchymal transformation and its role in renal fibrosis. J Gannan Med Univ. 44:634–640. 2024.

44 

Zhang L, Shen ZY, Wang K, Li W, Shi JM, Osoro EK, Ullah N, Zhou Y and Ji SR: C-reactive protein exacerbates epithelial-mesenchymal transition through Wnt/β-catenin and ERK signaling in streptozocin-induced diabetic nephropathy. FASEB J. 33:6551–6563. 2019. View Article : Google Scholar : PubMed/NCBI

45 

Teng S, Liu G, Li L, Ou J and Yu Y: CUX1 promotes epithelial-mesenchymal transition (EMT) in renal fibrosis of UUO model by targeting MMP7. Biochem Biophys Res Commun. 608:128–134. 2022. View Article : Google Scholar : PubMed/NCBI

46 

Juin SK, Pushpakumar S, Tyagi SC and Sen U: Glucosidase inhibitor, Nimbidiol ameliorates renal fibrosis and dysfunction in type-1 diabetes. Sci Rep. 12:217072022. View Article : Google Scholar : PubMed/NCBI

47 

Yang G, Zhao Z, Zhang X, Wu A, Huang Y, Miao Y and Yang M: Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice. Drug Des Devel Ther. 11:1065–1079. 2017. View Article : Google Scholar : PubMed/NCBI

48 

Li Z, Feng J, Zhong J, Lu M, Gao X and Zhang Y: Screening of the key genes and signalling pathways for diabetic nephropathy using bioinformatics analysis. Front Endocrinol (Lausanne). 13:8644072022. View Article : Google Scholar : PubMed/NCBI

49 

Gui H, Chen X, Ye L and Ma H: Seven basement membrane-specific expressed genes are considered potential biomarkers for the diagnosis and treatment of diabetic nephropathy. Acta Diabetol. 60:493–505. 2023. View Article : Google Scholar

50 

Speziale P, Arciola CR and Pietrocola G: Fibronectin and its role in human infective diseases. Cells. 8:15162019. View Article : Google Scholar : PubMed/NCBI

51 

Patten J and Wang K: Fibronectin in development and wound healing. Adv Drug Deliv Rev. 170:353–368. 2021. View Article : Google Scholar : PubMed/NCBI

52 

Zhang H, Chen X, Xue P, Ma X, Li J and Zhang J: FN1 promotes chondrocyte differentiation and collagen production via TGF-β/PI3K/Akt pathway in mice with femoral fracture. Gene. 769:1452532021. View Article : Google Scholar : PubMed/NCBI

53 

Yen CY, Huang CY, Hou MF, Yang YH, Chang CH, Huang HW, Chen CH and Chang HW: Evaluating the performance of fibronectin 1 (FN1), integrin α4β1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 as the potential biomarkers of oral squamous cell carcinoma (OSCC). Biomarkers. 18:63–72. 2013. View Article : Google Scholar : PubMed/NCBI

54 

Ma LJ, Lee SW, Lin LC, Chen TJ, Chang IW, Hsu HP, Chang KY, Huang HY and Li CF: Fibronectin overexpression is associated with latent membrane protein 1 expression and has independent prognostic value for nasopharyngeal carcinoma. Tumour Biol. 35:1703–1712. 2013. View Article : Google Scholar

55 

Lou X, Han X, Jin C, Tian W, Yu W, Ding D, Cheng L, Huang B, Jiang H and Lin B: SOX2 targets fibronectin 1 to promote cell migration and invasion in ovarian cancer: New molecular leads for therapeutic intervention. OMICS. 17:510–518. 2013. View Article : Google Scholar : PubMed/NCBI

56 

Waalkes S, Atschekzei F, Kramer MW, Hennenlotter J, Vetter G, Becker JU, Stenzl A, Merseburger AS, Schrader AJ, Kuczyk MA and Serth J: Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer. BMC Cancer. 10:5032010. View Article : Google Scholar : PubMed/NCBI

57 

Cai X, Liu C, Zhang TN, Zhu YW, Dong X and Xue P: Down-regulation of FN1 inhibits colorectal carcinogenesis by suppressing proliferation, migration and invasion. J Cell Biochem. 119:4717–4728. 2017. View Article : Google Scholar

58 

Zhou LT, Qiu S, Lv LL, Li ZL, Liu H, Tang RN, Ma KL and Liu BC: Integrative bioinformatics analysis provides insight into the molecular mechanisms of chronic kidney disease. Kidney Blood Press Res. 43:568–581. 2018. View Article : Google Scholar : PubMed/NCBI

59 

Chowdhury B, Zhang Z and Mukherjee AB: Uteroglobin interacts with the heparin-binding site of fibronectin and prevents fibronectin-IgA complex formation found in IgA-nephropathy. FEBS Lett. 582:611–615. 2008. View Article : Google Scholar

60 

Stehr AM, Wang G, Demmler R, Stemmler MP, Krug J, Tripal P, Schmid B, Geppert CI, Hartmann A, Muñoz LE, et al: Neutrophil extracellular traps drive epithelial-mesenchymal transition of human colon cancer. J Pathol. 256:455–467. 2022. View Article : Google Scholar

61 

Brabletz T, Kalluri R, Nieto MA and Weinberg RA: EMT in cancer. Nat Rev Cancer. 18:128–134. 2018. View Article : Google Scholar : PubMed/NCBI

62 

Li B, Shen W, Peng H, Li Y, Chen F, Zheng L, Xu J and Jia L: Fibronectin 1 promotes melanoma proliferation and metastasis by inhibiting apoptosis and regulating EMT. Onco Targets Ther. 12:3207–3221. 2019. View Article : Google Scholar : PubMed/NCBI

63 

Dallas SL, Keene DR, Bruder SP, Saharinen J, Sakai LY, Mundy GR and Bonewald LF: Role of the latent transforming growth factor beta binding protein 1 in fibrillin-containing microfibrils in bone cells in vitro and in vivo. J Bone Miner Res. 15:68–81. 2000. View Article : Google Scholar : PubMed/NCBI

64 

Dallas SL, Sivakumar P, Jones CJ, Chen Q, Peters DM, Mosher DF, Humphries MJ and Kielty CM: Fibronectin regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1. J Biol Chem. 280:18871–18880. 2005. View Article : Google Scholar : PubMed/NCBI

65 

Massagué J: Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 15:740–746. 2003. View Article : Google Scholar

66 

Derynck R and Akhurst RJ: Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol. 9:1000–1004. 2007. View Article : Google Scholar

67 

Hills CE and Squires PE: The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev. 22:131–139. 2011. View Article : Google Scholar : PubMed/NCBI

68 

Griggs LA, Hassan NT, Malik RS, Griffin BP, Martinez BA, Elmore LW and Lemmon CA: Fibronectin fibrils regulate TGF-β1-induced Epithelial-Mesenchymal transition. Matrix Biol. 60-61:157–175. 2017. View Article : Google Scholar

69 

Yu SM and Bonventre JV: Acute kidney injury and progression of diabetic kidney disease. Adv Chronic Kidney Dis. 25:166–180. 2018. View Article : Google Scholar : PubMed/NCBI

70 

Wada J and Makino H: Innate immunity in diabetes and diabetic nephropathy. Nat Rev Nephrol. 12:13–26. 2016. View Article : Google Scholar

71 

Zhu HM, Liu N, Sun DX and Luo L: Machine-learning algorithm-based prediction of a diagnostic model based on oxidative stress-related genes involved in immune infiltration in diabetic nephropathy patients. Front Immunol. 14:12022982023. View Article : Google Scholar

72 

Xu M, Zhou H, Hu P, Pan Y, Wang S, Liu L and Liu X: Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning. Front Immunol. 14:10845312023. View Article : Google Scholar

73 

Ji L, Chen Y, Wang H, Zhang W, He L, Wu J and Liu Y: Overexpression of Sirt6 promotes M2 macrophage transformation, alleviating renal injury in diabetic nephropathy. Int J Oncol. 55:103–115. 2019. View Article : Google Scholar

74 

Chow F, Ozols E, Nikolic-Paterson DJ, Atkins RC and Tesch GH: Macrophages in mouse type 2 diabetic nephropathy: Correlation with diabetic state and progressive renal injury. Kidney Int. 65:116–128. 2004. View Article : Google Scholar

75 

Tesch GH: Macrophages and diabetic nephropathy. Semin Nephrol. 30:290–301. 2010. View Article : Google Scholar

76 

Hofkens W, Storm G, Berg WVD and Lent PV: Inhibition of M1 macrophage activation in favour of M2 differentiation by liposomal targeting of glucocorticoids to the synovial lining during experimental arthritis. Ann Rheum Dis. 70 (Suppl 2):S702011. View Article : Google Scholar

77 

Gordon S: Alternative activation of macrophages. Nat Rev Immunol. 3:23–35. 2003. View Article : Google Scholar

78 

Kim H, Kim1 M, Lee HY, Park HY, Jhun H and Kim S: Role of dendritic cell in diabetic nephropathy. Int J Mol Sci. 22:75542021. View Article : Google Scholar

79 

Li HD, You YK, Shao BY, Wu WF, Wang YF, Guo JB, Meng XM and Chen H: Roles and crosstalks of macrophages in diabetic nephropathy. Front Immunol. 13:10151422022. View Article : Google Scholar

80 

Liang D, Liu L, Qi Y, Nan F, Huang J, Tang S, Tang J and Chen N: Jin-Gui-Shen-Qi Wan alleviates fibrosis in mouse diabetic nephropathy via MHC class II. J Ethnopharmacol. 324:1177452024. View Article : Google Scholar

81 

Zhou Y, Luo Z, Liao C, Cao R, Hussain Z, Wang J, Zhou Y, Chen T, Sun J, Huang Z, et al: MHC class II in renal tubules plays an essential role in renal fibrosis. Cell Mol Immunol. 18:2530–2540. 2021. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tang H, Li K and Wang X: Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning. Mol Med Rep 32: 249, 2025.
APA
Tang, H., Li, K., & Wang, X. (2025). Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning. Molecular Medicine Reports, 32, 249. https://doi.org/10.3892/mmr.2025.13614
MLA
Tang, H., Li, K., Wang, X."Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning". Molecular Medicine Reports 32.3 (2025): 249.
Chicago
Tang, H., Li, K., Wang, X."Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning". Molecular Medicine Reports 32, no. 3 (2025): 249. https://doi.org/10.3892/mmr.2025.13614
Copy and paste a formatted citation
x
Spandidos Publications style
Tang H, Li K and Wang X: Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning. Mol Med Rep 32: 249, 2025.
APA
Tang, H., Li, K., & Wang, X. (2025). Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning. Molecular Medicine Reports, 32, 249. https://doi.org/10.3892/mmr.2025.13614
MLA
Tang, H., Li, K., Wang, X."Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning". Molecular Medicine Reports 32.3 (2025): 249.
Chicago
Tang, H., Li, K., Wang, X."Identification and validation of epithelial‑mesenchymal transition‑related genes for diabetic nephropathy by WGCNA and machine learning". Molecular Medicine Reports 32, no. 3 (2025): 249. https://doi.org/10.3892/mmr.2025.13614
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team