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
October-2018 Volume 18 Issue 4

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
October-2018 Volume 18 Issue 4

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 Open Access

Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway

  • Authors:
    • Yanwu Sun
    • Yiyi Zhang
    • Pan Chi
  • View Affiliations / Copyright

    Affiliations: Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3907-3913
    |
    Published online on: August 22, 2018
       https://doi.org/10.3892/mmr.2018.9423
  • 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

Intestinal fibroblasts, the main effector cells of intestinal fibrosis, are considered to be a good target for anti‑fibrotic therapy. The aim of the present study was to examine the effects of pirfenidone (PFD) on human intestinal fibroblasts (HIFs) stimulated by transforming growth factor (TGF)‑β1 and to explore the potential mechanism. Prior to stimulation with TGF‑β1 (10 ng/ml), HIFs were treated with or without PFD (1 mg/ml). Cell proliferation was determined by Cell Counting Kit (CCK)‑8 and colony formation assays, and cell apoptosis was assessed using flow cytometry and a TUNEL assay. Reverse transcription‑quantitative polymerase chain reaction and western blotting were performed to evaluate the mRNA and protein expressions of α‑smooth muscle actin (α‑SMA), collagen I and fibronectin. The protein expression of TGF‑β1/mothers against decapentaplegic homolog (Smad) and phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathways was evaluated by western blotting. CCK‑8 and colony formation assays demonstrated that PFD significantly inhibited cell proliferation in HIFs stimulated with TGF‑β1. Flow cytometry and TUNEL assays revealed that PFD treatment significantly enhanced apoptosis in TGF‑β1‑stimulated HIFs. In addition, PFD markedly reduced TGF‑β1‑induced HIF activities, such as myofibroblast differentiation (α‑SMA), and collagen production (collagen I and fibronectin). These effects of PFD were mediated by the inhibition of the TGF‑β1/Smad and PI3K/AKT signaling pathways. Therefore, the present study demonstrated that PFD reduced TGF‑β1‑induced fibrogenic activities of HIFs, suggesting that PFD may be a potential therapeutic agent for intestinal fibrosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Rieder F and Fiocchi C: Intestinal fibrosis in IBD-a dynamic, multifactorial process. Nat Rev Gastroenterol Hepatol. 6:228–235. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Stacey R and Green JT: Radiation-induced small bowel disease: Latest developments and clinical guidance. Ther Adv Chronic Dis. 5:15–29. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Hamama S, Delanian S, Monceau V and Vozenin MC: Therapeutic management of intestinal fibrosis induced by radiation therapy: From molecular profiling to new intervention strategies et vice et versa. Fibrogenesis Tissue Repair. 5 Suppl 1:S132012.PubMed/NCBI

4 

Kendall RT and Feghali-Bostwick CA: Fibroblasts in fibrosis: Novel roles and mediators. Front Pharmacol. 5:1232014. View Article : Google Scholar : PubMed/NCBI

5 

Zeisberg M and Kalluri R: Cellular mechanisms of tissue fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis. Am J Physiol Cell Physiol. 304:C216–C225. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Speca S, Giusti I, Rieder F and Latella G: Cellular and molecular mechanisms of intestinal fibrosis. World J Gastroenterol. 18:3635–3661. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Meng XM, Nikolic-Paterson DJ and Lan HY: TGF-β: The master regulator of fibrosis. Nat Rev Nephrol. 12:325–338. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Li Y, Liu H, Liang Y, Peng P, Ma X and Zhang X: DKK3 regulates cell proliferation, apoptosis and collagen synthesis in keloid fibroblasts via TGF-β1/Smad signaling pathway. Biomed Pharmacother. 91:174–180. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Conte E, Gili E, Fagone E, Fruciano M, Iemmolo M and Vancheri C: Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts. Eur J Pharm Sci. 58:13–19. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Abe Y, Murano M, Murano N, Morita E, Inoue T, Kawakami K, Ishida K, Kuramoto T, Kakimoto K, Okada T, et al: Simvastatin attenuates intestinal fibrosis independent of the anti-inflammatory effect by promoting fibroblast/myofibroblast apoptosis in the regeneration/healing process from TNBS-induced colitis. Dig Dis Sci. 57:335–344. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, Taguchi Y, Nagai S, Itoh H, Ohi M, et al: Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 171:1040–1047. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Di Sario A, Bendia E, Svegliati Baroni G, Ridolfi F, Casini A, Ceni E, Saccomanno S, Marzioni M, Trozzi L, Sterpetti P, et al: Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production. J Hepatol. 37:584–591. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Miric G, Dallemagne C, Endre Z, Margolin S, Taylor SM and Brown L: Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin-diabetic rat. Br J Pharmacol. 133:687–694. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Shi Q, Liu X, Bai Y, Cui C, Li J, Li Y, Hu S and Wei Y: In vitro effects of pirfenidone on cardiac fibroblasts: Proliferation, myofibroblast differentiation, migration and cytokine secretion. PLoS One. 6:e281342011. View Article : Google Scholar : PubMed/NCBI

15 

Duan L, Qi J, Huang T, Gu X, Xu D, Kong X and Qian XQ: Pirfenidone attenuates bladder fibrosis and mitigates deterioration of bladder function in a rat model of partial bladder outlet obstruction. Mol Med Rep. 12:3639–3647. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Lin X, Yu M, Wu K, Yuan H and Zhong H: Effects of pirfenidone on proliferation, migration, and collagen contraction of human Tenon's fibroblasts in vitro. Invest Ophthalmol Vis Sci. 50:3763–3770. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Hewitson TD, Kelynack KJ, Tait MG, Martic M, Jones CL, Margolin SB and Becker GJ: Pirfenidone reduces in vitro rat renal fibroblast activation and mitogenesis. J Nephrol. 14:453–460. 2001.PubMed/NCBI

18 

Chan AL, Rafii R, Louie S and Albertson TE: Therapeutic update in idiopathic pulmonary fibrosis. Clin Rev Allergy Immunol. 44:65–74. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Cottin V: The role of pirfenidone in the treatment of idiopathic pulmonary fibrosis. Respir Res. 14 Suppl 1:S52013.PubMed/NCBI

20 

Takeda Y, Tsujino K, Kijima T and Kumanogoh A: Efficacy and safety of pirfenidone for idiopathic pulmonary fibrosis. Patient Prefer Adherence. 8:361–370. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Meier R, Lutz C, Cosín-Roger J, Fagagnini S, Bollmann G, Hünerwadel A, Mamie C, Lang S, Tchouboukov A, Weber FE, et al: Decreased fibrogenesis after treatment with pirfenidone in a newly developed mouse model of intestinal fibrosis. Inflamm Bowel Dis. 22:569–582. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Li G, Ren J, Hu Q, Deng Y, Chen G, Guo K, Li R, Li Y, Wu L, Wang G, et al: Oral pirfenidone protects against fibrosis by inhibiting fibroblast proliferation and TGF-β signaling in a murine colitis model. Biochem Pharmacol. 117:57–67. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Sun YW, Zhang YY, Ke XJ, Wu XJ, Chen ZF and Chi P: Pirfenidone prevents radiation-induced intestinal fibrosis in rats by inhibiting fibroblast proliferation and differentiation and suppressing the TGF-β1/Smad/CTGF signaling pathway. Eur J Pharmacol. 822:199–206. 2018. View Article : Google Scholar : PubMed/NCBI

24 

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

25 

Ni BB, Li B, Yang YH, Chen JW, Chen K, Jiang SD and Jiang LS: The effect of transforming growth factor β1 on the crosstalk between autophagy and apoptosis in the annulus fibrosus cells under serum deprivation. Cytokine. 70:87–96. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Wu L, Zhang Q, Mo W, Feng J, Li S, Li J, Liu T, Xu S, Wang W, Lu X, et al: Quercetin prevents hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing autophagy via the TGF-β1/Smads and PI3K/Akt pathways. Sci Rep. 7:92892017. View Article : Google Scholar : PubMed/NCBI

27 

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

28 

Lee BS, Margolin SB and Nowak RA: Pirfenidone: A novel pharmacological agent that inhibits leiomyoma cell proliferation and collagen production. J Clin Endocrinol Metab. 83:219–223. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Luna J, Masamunt MC, Lawrance IC and Sans M: Mesenchymal cell proliferation and programmed cell death: Key players in fibrogenesis and new targets for therapeutic intervention. Am J Physiol Gastrointest Liver Physiol. 300:G703–G708. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Choi K, Lee K, Ryu SW, Im M, Kook KH and Choi C: Pirfenidone inhibits transforming growth factor-β1-induced fibrogenesis by blocking nuclear translocation of Smads in human retinal pigment epithelial cell line ARPE-19. Mol Vis. 18:1010–1020. 2012.PubMed/NCBI

32 

Downward J: PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol. 15:177–182. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Sun Y, Zhang Y and Chi P: Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway. Mol Med Rep 18: 3907-3913, 2018.
APA
Sun, Y., Zhang, Y., & Chi, P. (2018). Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway. Molecular Medicine Reports, 18, 3907-3913. https://doi.org/10.3892/mmr.2018.9423
MLA
Sun, Y., Zhang, Y., Chi, P."Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway". Molecular Medicine Reports 18.4 (2018): 3907-3913.
Chicago
Sun, Y., Zhang, Y., Chi, P."Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway". Molecular Medicine Reports 18, no. 4 (2018): 3907-3913. https://doi.org/10.3892/mmr.2018.9423
Copy and paste a formatted citation
x
Spandidos Publications style
Sun Y, Zhang Y and Chi P: Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway. Mol Med Rep 18: 3907-3913, 2018.
APA
Sun, Y., Zhang, Y., & Chi, P. (2018). Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway. Molecular Medicine Reports, 18, 3907-3913. https://doi.org/10.3892/mmr.2018.9423
MLA
Sun, Y., Zhang, Y., Chi, P."Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway". Molecular Medicine Reports 18.4 (2018): 3907-3913.
Chicago
Sun, Y., Zhang, Y., Chi, P."Pirfenidone suppresses TGF‑β1‑induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway". Molecular Medicine Reports 18, no. 4 (2018): 3907-3913. https://doi.org/10.3892/mmr.2018.9423
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