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
December-2016 Volume 14 Issue 6

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
December-2016 Volume 14 Issue 6

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
Article

PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition

  • Authors:
    • Xiao‑Ling Zhang
    • Rong‑Ge Xing
    • Liang Chen
    • Chun‑Rong Liu
    • Zhi‑Gang Miao
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
  • Pages: 5699-5706
    |
    Published online on: November 22, 2016
       https://doi.org/10.3892/mmr.2016.5960
  • 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

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by chronic inflammation, fibroblast proliferation and extracellular matrix deposition. However, the molecular and cellular mechanisms underlying the pathogenesis of pulmonary fibrosis remain to be fully elucidated. The contribution of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway in fibrotic processes remains to be investigated. The aim of the present study was to investigate the role of the PI3K/Akt pathway in pulmonary fibrosis. A rat model of pulmonary fibrosis was induced by intratracheal administration of bleomycin (BLM), and a specific PI3K/Akt inhibitor, LY294002, was used to assess the role of the PI3K/Akt pathway in fibrogenesis. The inflammatory and fibrotic alterations in the lung tissues were evaluated using histological staining and the hydroxyproline assay. In addition, the concentration of cytokines in bronchoalveolar lavage fluid and the expression of Akt, phosphorylated (p‑)Akt, epithelial cadherin, α smooth muscle actin and vimentin in lung tissues. The data demonstrated that an increase in the expression levels of p‑Akt was involved in the progression of pulmonary fibrosis and contributed to fibrogenesis. Administration of the Akt inhibitor significantly attenuated inflammation and fibrosis, which was accompanied by a reversal of lung fibrosis‑associated epithelial‑mesenchymal transition. Taken together, these observations suggest that the PI3K/Akt pathway serves a central role in the pathophysiology of lung fibrosis, and is a promising therapeutic target.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Guiot J, Corhay JL and Louis R: Idiopathic pulmonary fibrosis. Rev Med Liege. 69:605–610. 2014.PubMed/NCBI

2 

Kim HJ, Perlman D and Tomic R: Natural history of idiopathic pulmonary fibrosis. Respir Med. 109:661–670. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Gharaee-Kermani M, Gyetko MR, Hu B and Phan SH: New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: A potential role for stem cells in the lung parenchyma and implications for therapy. Pharm Res. 24:819–841. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Fernandez IE and Eickelberg O: New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet. 380:680–688. 2012. View Article : Google Scholar : PubMed/NCBI

5 

King TE Jr, Pardo A and Selman M: Idiopathic pulmonary fibrosis. Lancet. 378:1949–1961. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Yan W, Xiaoli L, Guoliang A, Zhonghui Z, Di L, Ximeng L, Piye N, Li C and Lin T: SB203580 inhibits epithelial-mesenchymal transition and pulmonary fibrosis in a rat silicosis model. Toxicol Lett. 259:28–34. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Harrison JH Jr and Lazo JS: High dose continuous infusion of bleomycin in mice: A new model for drug-induced pulmonary fibrosis. J Pharmacol Exp Ther. 243:1185–1194. 1987.PubMed/NCBI

8 

Moeller A, Ask K, Warburton D, Gauldie J and Kolb M: The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int J Biochem Cell Biol. 40:362–382. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Adamson IY and Bowden DH: The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol. 77:185–197. 1974.PubMed/NCBI

10 

Moore BB and Hogaboam CM: Murine models of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 294:L152–L160. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Kim HS, Go H, Akira S and Chung DH: TLR2-mediated production of IL-27 and chemokines by respiratory epithelial cells promotes bleomycin-induced pulmonary fibrosis in mice. J Immunol. 187:4007–4017. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Degryse AL, Tanjore H, Xu XC, Polosukhin VV, Jones BR, Boomershine CS, Ortiz C, Sherrill TP, McMahon FB, Gleaves LA, et al: TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment. Am J Physiol Lung Cell Mol Physiol. 300:L887–L897. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Chen YL, Zhang X, Bai J, Gai L, Ye XL, Zhang L, Xu Q, Zhang YX, Xu L, Li HP and Ding X: Sorafenib ameliorates bleomycin-induced pulmonary fibrosis: Potential roles in the inhibition of epithelial-mesenchymal transition and fibroblast activation. Cell Death Dis. 4:e6652013. View Article : Google Scholar : PubMed/NCBI

14 

Yin MM, Cui YR, Wang L, Wang JY, Gao Y and Xi JY: Progress on PI3K/Akt signaling pathway regulating self-renewal and pluripotency of embryonic stem cells. Sheng Li Xue Bao. 66:223–230. 2014.(In Chinese). PubMed/NCBI

15 

Diehl N and Schaal H: Make yourself at home: Viral hijacking of the PI3K/Akt signaling pathway. Viruses. 5:3192–3212. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Diab S, Fidanzi C, Léger DY, Ghezali L, Millot M, Martin F, Azar R, Esseily F, Saab A, Sol V, et al: Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis. Int J Oncol. 47:220–230. 2015.PubMed/NCBI

17 

Ribback S, Cigliano A, Kroeger N, Pilo MG, Terracciano L, Burchardt M, Bannasch P, Calvisi DF and Dombrowski F: PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tubules of rats and men. Oncotarget. 30:13036–13048. 2015. View Article : Google Scholar

18 

Xu X, Li H, Hou X, Li D, He S, Wan C, Yin P, Liu M, Liu F and Xu J: Punicalagin induces Nrf2/HO-1 expression via upregulation of PI3K/AKT pathway and inhibits LPS-induced oxidative stress in RAW264.7 macrophages. Mediators Inflamm. 2015:3802182015. View Article : Google Scholar : PubMed/NCBI

19 

Chen H, Mei YQ and Solomon MA: Experiences of establishing an abdominal heart transplantation model in rats. Zhonghua Yi Xue Za Zhi. 92:1715–1718. 2012.(In Chinese). PubMed/NCBI

20 

Szapiel SV, Elson NA, Fulmer JD, Hunninghake GW and Crystal RG: Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis. 120:893–899. 1979.PubMed/NCBI

21 

Huang LS, Berdyshev E, Mathew B, Fu P, Gorshkova IA, He D, Ma W, Noth I, Ma SF, Pendyala S, et al: Targeting sphingosine kinase 1 attenuates bleomycin-induced pulmonary fibrosis. FASEB J. 27:1749–1760. 2013. View Article : Google Scholar : PubMed/NCBI

22 

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

23 

Mabuchi S, Kuroda H, Takahashi R and Sasano T: The PI3K/AKT/mTOR pathway as a therapeutic target in ovarian cancer. Gynecol Oncol. 137:173–179. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Lee SJ, Kim KH and Park KK: Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition. World J Hepatol. 6:207–216. 2014. View Article : Google Scholar : PubMed/NCBI

25 

O'Connor JW and Gomez EW: Biomechanics of TGFβ-induced epithelial-mesenchymal transition: Implications for fibrosis and cancer. Clin Transl Med. 3:232014. View Article : Google Scholar : PubMed/NCBI

26 

Takano M, Yamamoto C, Yamaguchi K, Kawami M and Yumoto R: Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3. Drug Metab Pharmacokinet. 30:111–118. 2015. View Article : Google Scholar : PubMed/NCBI

27 

PLOS ONE Staff, . Correction: Melatonin inhibits endoplasmic reticulum stress and epithelial-mesenchymal transition during bleomycin-induced pulmonary fibrosis in mice. PloS One. 10:e01193812015. View Article : Google Scholar : PubMed/NCBI

28 

Zhou N, Lu F, Liu C, Xu K, Huang J, Yu D and Bi L: IL-8 induces the epithelial-mesenchymal transition of renal cell carcinoma cells through the activation of AKT signaling. Oncol Lett. 12:1915–1920. 2016.PubMed/NCBI

29 

Shan B, Man H, Liu J, Wang L, Zhu T, Ma M, Xv Z, Chen X, Yang X and Li P: TIM-3 promotes the metastasis of esophageal squamous cell carcinoma by targeting epithelial-mesenchymal transition via the Akt/GSK-3β/Snail signaling pathway. Oncol Rep. 36:1551–1561. 2016.PubMed/NCBI

30 

Yi GZ, Liu YW, Xiang W, Wang H, Chen ZY, Xie SD and Qi ST: Akt and β-catenin contribute to TMZ resistance and EMT of MGMT negative malignant glioma cell line. J Neurol Sci. 367:101–106. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang XL, Xing RG, Chen L, Liu CR and Miao ZG: PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition. Mol Med Rep 14: 5699-5706, 2016.
APA
Zhang, X., Xing, R., Chen, L., Liu, C., & Miao, Z. (2016). PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition. Molecular Medicine Reports, 14, 5699-5706. https://doi.org/10.3892/mmr.2016.5960
MLA
Zhang, X., Xing, R., Chen, L., Liu, C., Miao, Z."PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition". Molecular Medicine Reports 14.6 (2016): 5699-5706.
Chicago
Zhang, X., Xing, R., Chen, L., Liu, C., Miao, Z."PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition". Molecular Medicine Reports 14, no. 6 (2016): 5699-5706. https://doi.org/10.3892/mmr.2016.5960
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang XL, Xing RG, Chen L, Liu CR and Miao ZG: PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition. Mol Med Rep 14: 5699-5706, 2016.
APA
Zhang, X., Xing, R., Chen, L., Liu, C., & Miao, Z. (2016). PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition. Molecular Medicine Reports, 14, 5699-5706. https://doi.org/10.3892/mmr.2016.5960
MLA
Zhang, X., Xing, R., Chen, L., Liu, C., Miao, Z."PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition". Molecular Medicine Reports 14.6 (2016): 5699-5706.
Chicago
Zhang, X., Xing, R., Chen, L., Liu, C., Miao, Z."PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition". Molecular Medicine Reports 14, no. 6 (2016): 5699-5706. https://doi.org/10.3892/mmr.2016.5960
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