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Article Open Access

Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods

  • Authors:
    • Wan-Ning Wang
    • Wen-Long Zhang
    • Guang-Yu Zhou
    • Fu-Zhe Ma
    • Tao Sun
    • Sen-Sen Su
    • Zhong-Gao Xu
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1181-1188
    |
    Published online on: March 15, 2016
       https://doi.org/10.3892/ijmm.2016.2527
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Abstract

In this study, we aimed to explore the molecular mechanisms of and genetic factors influencing diabetic nephropathy (DN). Gene expression profiles associated with DN were obtained from the GEO database (Accession no. GSE20844). The differentially expressed genes (DEGs) between diabetic mice and non-diabetic mice were screened. Subsequently, the DEGs were subjected to functional and pathway analysis. The protein-protein interaction (PPI) network was constructed and the transcription factors (TFs) were screened among the DEGs. A total of 92 upregulated and 118 downregulated genes were screened. Pathway analysis revealed that the p53 signaling pathway, the transforming growth factor (TGF)-β signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway were significantly enriched by upregulated genes. Serpine1 (also known as plasminogen activator inhibitor-1), early growth response 1 (Egr1) and Mdk were found to be significant nodes in the PPI network by three methods. A total of 12 TFs were found to be differentially expressed, of which nuclear receptor subfamily 4, group A, member 1 (Nr4a1) and peroxisome proliferator-activated receptor gamma (Pparg) were found to have multiple interactions with other DEGs. We demonstrated that the p53 signaling pathway, the TGF-β signaling pathway and the MAPK signaling pathway were dysregulated in the diabetic mice. The significant nodes (Serpine1, Egr1 and Mdk) and differentially expressed TFs (Nr4a1 and Pparg) may provide a novel avenue for the targeted therapy of DN.
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1 

Sun YM, Su Y, Li J and Wang LF: Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy. Biochem Biophys Res Commun. 433:359–361. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML and Zelmanovitz T: Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care. 28:164–176. 2005. View Article : Google Scholar

3 

Navarro-González JF, Mora-Fernández C, Muros de Fuentes M and García-Pérez J: Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 7:327–340. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Luis-Rodríguez D, Martínez-Castelao A, Górriz JL, De-Álvaro F and Navarro-González JF: Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy. World J Diabetes. 3:7–18. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Xie X, Peng J, Chang X, Huang K, Huang J, Wang S, Shen X, Liu P and Huang H: Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy. Mol Cell Endocrinol. 369:86–97. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet J-P, Subramanian A, Ross KN, et al: The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 313:1929–1935. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Reiniger N, Lau K, McCalla D, Eby B, Cheng B, Lu Y, Qu W, Quadri N, Ananthakrishnan R, Furmansky M, et al: Deletion of the receptor for advanced glycation end products reduces glomerulosclerosis and preserves renal function in the diabetic OVE26 mouse. Diabetes. 59:2043–2054. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Gautier L, Cope L, Bolstad BM and Irizarry RA: affy-analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 20:307–315. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Smyth GK: limma: linear models for microarray data. Bioinformatics and Computational Biology Solutions Using R and Bioconductor. Gentleman R, Carey VJ, Huber W, Irizarry RA and Dudoit S: Springer; New York, NY: pp. 397–420. 2005, View Article : Google Scholar

10 

Huang W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar

11 

Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, et al: STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43:D447–D452. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Tang Y, Li M, Wang J, Pan Y and Wu FX: CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems. 127:67–72. 2015. View Article : Google Scholar

13 

Jeong H, Mason SP, Barabási AL and Oltvai ZN: Lethality and centrality in protein networks. Nature. 411:41–42. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Goh KI, Oh E, Kahng B and Kim D: Betweenness centrality correlation in social networks. Phys Rev E Stat Nonlin Soft Matter Phys. 67:0171012003. View Article : Google Scholar : PubMed/NCBI

15 

Estrada E and Rodríguez-Velázquez JA: Subgraph centrality in complex networks. Phys Rev E Stat Nonlin Soft Matter Phys. 71:0561032005. View Article : Google Scholar : PubMed/NCBI

16 

Zhang HM, Liu T, Liu CJ, Song S, Zhang X, Liu W, Jia H, Xue Y and Guo AY: AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors. Nucleic Acids Res. 43:D76–D81. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Janky R, Verfaillie A, Imrichová H, Van de Sande B, Standaert L, Christiaens V, Hulselmans G, Herten K, Naval Sanchez M, Potier D, et al: iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLoS Comput Biol. 10:e10037312014. View Article : Google Scholar : PubMed/NCBI

18 

Go AS, Chertow GM, Fan D, McCulloch CE and Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 351:1296–1305. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Pfeffer MA, Burdmann EA, Chen C-Y, Cooper ME, de Zeeuw D, Eckardt K-U, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, et al: TREAT Investigators: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 361:2019–2032. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Deshpande SD, Putta S, Wang M, Lai JY, Bitzer M, Nelson RG, Lanting LL, Kato M and Natarajan R: Transforming growth factor-β-induced cross talk between p53 and a microRNA in the pathogenesis of diabetic nephropathy. Diabetes. 62:3151–3162. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Fang Y, Tian X, Bai S, Fan J, Hou W, Tong H and Li D: Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway. Int J Mol Med. 30:85–92. 2012.PubMed/NCBI

22 

Adhikary L, Chow F, Nikolic-Paterson DJ, Stambe C, Dowling J, Atkins RC and Tesch GH: Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy. Diabetologia. 47:1210–1222. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Oda T, Jung YO, Kim HS, Cai X, López-Guisa JM, Ikeda Y and Eddy AA: PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction. Kidney Int. 60:587–596. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Kitching AR, Kong YZ, Huang XR, Davenport P, Edgtton KL, Carmeliet P, Holdsworth SR and Tipping PG: Plasminogen activator inhibitor-1 is a significant determinant of renal injury in experimental crescentic glomerulonephritis. J Am Soc Nephrol. 14:1487–1495. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Alvarez ML and DiStefano JK: Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy. PLoS One. 6:e186712011. View Article : Google Scholar : PubMed/NCBI

26 

Rerolle JP, Hertig A, Nguyen G, Sraer JD and Rondeau EP: Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis. Kidney Int. 58:1841–1850. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Lassila M, Fukami K, Jandeleit-Dahm K, Semple T, Carmeliet P, Cooper ME and Kitching AR: Plasminogen activator inhibitor-1 production is pathogenetic in experimental murine diabetic renal disease. Diabetologia. 50:1315–1326. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Kosugi T and Sato W: Midkine and the kidney: health and diseases. Nephrol Dial Transplant. 27:16–21. 2012. View Article : Google Scholar

29 

Gil N, Goldberg R, Neuman T, Garsen M, Zcharia E, Rubinstein AM, van Kuppevelt T, Meirovitz A, Pisano C, Li JP, et al: Heparanase is essential for the development of diabetic nephropathy in mice. Diabetes. 61:208–216. 2012. View Article : Google Scholar :

30 

McMorrow JP and Murphy EP: Inflammation: a role for NR4A orphan nuclear receptors? Biochem Soc Trans. 39:688–693. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Hagiwara S, Mcclelland A and Kantharidis P: MicroRNA in diabetic nephropathy: renin angiotensin, aGE/RAGE, and oxidative stress pathway. J Diabetes Res. 2013:1737832013. View Article : Google Scholar

32 

Westbrook L, Johnson AC, Regner KR, Williams JM, Mattson DL, Kyle PB, Henegar JR and Garrett MR: Genetic susceptibility and loss of Nr4a1 enhances macrophage-mediated renal injury in CKD. J Am Soc Nephrol. 25:2499–2510. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Lapice E, Pinelli M, Riccardi G and Vaccaro O: Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients: comment on the study Liu et al. Diabetes Care. 33:e114author reply e115. 2010. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Wang W, Zhang W, Zhou G, Ma F, Sun T, Su S and Xu Z: Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods. Int J Mol Med 37: 1181-1188, 2016.
APA
Wang, W., Zhang, W., Zhou, G., Ma, F., Sun, T., Su, S., & Xu, Z. (2016). Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods. International Journal of Molecular Medicine, 37, 1181-1188. https://doi.org/10.3892/ijmm.2016.2527
MLA
Wang, W., Zhang, W., Zhou, G., Ma, F., Sun, T., Su, S., Xu, Z."Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods". International Journal of Molecular Medicine 37.5 (2016): 1181-1188.
Chicago
Wang, W., Zhang, W., Zhou, G., Ma, F., Sun, T., Su, S., Xu, Z."Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods". International Journal of Molecular Medicine 37, no. 5 (2016): 1181-1188. https://doi.org/10.3892/ijmm.2016.2527
Copy and paste a formatted citation
x
Spandidos Publications style
Wang W, Zhang W, Zhou G, Ma F, Sun T, Su S and Xu Z: Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods. Int J Mol Med 37: 1181-1188, 2016.
APA
Wang, W., Zhang, W., Zhou, G., Ma, F., Sun, T., Su, S., & Xu, Z. (2016). Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods. International Journal of Molecular Medicine, 37, 1181-1188. https://doi.org/10.3892/ijmm.2016.2527
MLA
Wang, W., Zhang, W., Zhou, G., Ma, F., Sun, T., Su, S., Xu, Z."Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods". International Journal of Molecular Medicine 37.5 (2016): 1181-1188.
Chicago
Wang, W., Zhang, W., Zhou, G., Ma, F., Sun, T., Su, S., Xu, Z."Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods". International Journal of Molecular Medicine 37, no. 5 (2016): 1181-1188. https://doi.org/10.3892/ijmm.2016.2527
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