Skip to main content

Advertisement

SpringerLink
Log in

Rosiglitazone attenuates activation of human Tenon’s fibroblasts induced by transforming growth factor -β1

  • Glaucoma
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the influence of rosiglitazone on activation of human Tenon’s fibroblasts (HTFs) and to access the possible mechanism.

Methods

Cultured human Tenon’s fibroblasts were pretreated in two different concentrations of rosiglitazone (5 μmol/l and 10 μmol/l) before being stimulated with 5 ng/ml transforming growth factor β1 (TGF-β1). The viability and proliferation of cells were accessed by cell count kit-8 assay; Cell migration was examined by the wound closure assay; Alpha smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) and type I collagen (COL I) transcription were detected by RT-qPCR; The expression and localization of α-SMA protein were examined by Western-blot analysis and Immunofluorescence staining; Western-blot analysis was also used to check the expression of CTGF, COL I peroxisome proliferator-activated receptor gamma (PPAR-γ), and phosphorylation of the signaling protein Smad2/3

Results

Rosiglitazone is able to attenuate the up-regulation of α-SMA, CTGF, and COL I transcription, as well as affect protein expression, proliferation, and migration of cells; rosiglitazone also can increase PPAR-γ expression and attenuate Smad2/3 phosphorylation.

Conclusions

Rosiglitazone can effectively attenuate activation of HTFs induced by TGF-β1 without obvious toxicity. The possible mechanism might be that rosiglitazone interferes with TGF-β/Smad signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Lama PJ, Fechtner RD (2003) Antifibrotics and wound healing in glaucoma surgery. Surv Ophthalmol 48:314–346

    Article  PubMed  Google Scholar 

  2. Loon SC, Chew PT (1999) A major review of antimetabolites in glaucoma therapy. Ophthalmologica 213:234–245

    Article  PubMed  CAS  Google Scholar 

  3. Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214:199–210

    Article  PubMed  CAS  Google Scholar 

  4. Darby IA, Hewitson TD (2007) Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol 257:143–179

    Article  PubMed  CAS  Google Scholar 

  5. Saika S, Yamanaka O, Okada Y, Tanaka S, Miyamoto T, Sumioka T, Kitano A, Shirai K, Ikeda K (2009) TGFß in fibroproliferative diseases in the eye. Front Biosci (Schol Ed) 1:376–390

    Google Scholar 

  6. Cordeiro MF, Mead A, Ali RR, Alexander RA, Murray S, Chen C, York-Defalco C, Dean NM, Schultz GS, Khaw PT (2003) Novel antisense oligonucleotides targeting TGF-ß inhibit in vivo scarring and improve surgical outcome. Gene Ther 10:59–71

    Article  PubMed  CAS  Google Scholar 

  7. Cordeiro MF, Gay JA, Khaw PT (1999) Human anti-transforming growth factor-ß2 antibody: a new glaucoma anti-scarring agent. Invest Ophthalmol Vis Sci 40:2225–2234

    PubMed  CAS  Google Scholar 

  8. Grisanti S, Szurman P, Warga M (2005) Decorin modulates wound healing in experimental glaucoma filtration surgery: a pilot study. Invest Ophthalmol Vis Sci 46:191–196

    Article  PubMed  Google Scholar 

  9. Nakamura H, Siddiqui SS, Shen X, Malik AB, Pulido JS, Kumar NM, Yue BY (2004) RNA interference targeting transforming growth factor-ß type II receptor suppresses ocular inflammation and fibrosis. Mol Vis 10:703–711

    PubMed  CAS  Google Scholar 

  10. Derynck R, Zhang YE (2003) Smad-dependent and Samd-independent pathways in TGF-β family signaling. Nature 425:577–584

    Article  PubMed  CAS  Google Scholar 

  11. Saika S (2006) TGFß pathobiology in the eye. Lab Investig 86:106–115

    Article  PubMed  CAS  Google Scholar 

  12. Cho N, Momose Y (2008) Peroxisome proliferator-activated receptor γ agonists as insulin sensitizers: from the discovery to recent progress. Curr Top Med Chem 8:1483–1507

    Article  PubMed  CAS  Google Scholar 

  13. Chinetti G, Fruchart JC, Staels B (2000) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 49:497–505

    Article  PubMed  CAS  Google Scholar 

  14. Nakamoto M, Ohya Y, Shinzato T, Mano R, Yamazato M, Sakima A, Takishita S (2008) Pioglitazone, a thiazolidinedione derivative, attenuates left ventricular hypertrophy and fibrosis in salt-sensitive hypertension. Hypertens Res 31:353–361

    Article  PubMed  CAS  Google Scholar 

  15. Yu J, Zhang S, Chu ES, Go MY, Lau RH, Zhao J, Wu CW, Tong L, Zhao J, Poon TC, Sung JJ (2010) Peroxisome proliferator-activated receptors gamma reverses hepatic nutritional fibrosis in mice and suppresses activation of hepatic stellate cells in vitro. Int J Biochem Cell Biol 42:948–957

    Article  PubMed  CAS  Google Scholar 

  16. Jaster R, Lichte P, Fitzner B, Brock P, Glass A, Karopka T, Gierl L, Koczan D, Thiesen HJ, Sparmann G, Emmrich J, Liebe S (2005) Peroxisome proliferator-activated receptor γ overexpression inhibits pro-fibrogenic activities of immortalised rat pancreatic stellate cells. J Cell Mol Med 9:670–682

    Article  PubMed  CAS  Google Scholar 

  17. Burgess HA, Daugherty LE, Thatcher TH, Lakatos HF, Ray DM, Redonnet M, Phipps RP, Sime PJ (2005) PPAR gamma agonists inhibit TGF-ß induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol Lung Cell Mol Physiol 288:1146–1153

    Article  Google Scholar 

  18. Hinz B (2007) Formation and function of the myofibroblast during tissue repair. J Invest Dermatol 127:526–537

    Article  PubMed  CAS  Google Scholar 

  19. Guo B, Koya D, Isono M, Sugimoto T, Kashiwagi A, Haneda M (2004) Peroxisome proliferator-activated receptor-γ ligands inhibit TGF-ß1-induced fibronectin expression in glomerular mesangial cells. Diabetes 53:200–208

    Article  PubMed  CAS  Google Scholar 

  20. Wang W, Liu F, Chen N (2007) Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists attenuate the profibrotic response induced by TGF-ß1 in renal interstitial fibroblasts. Mediat Inflamm 2007:62641

    Google Scholar 

  21. Zhang GY, Cheng T, Zheng MH, Yi CG, Pan H, Li ZJ, Chen XL, Yu Q, Jiang LF, Zhou FY, Li XY, Yang JQ, Chu TG, Gao WY (2010) Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts. J Plast Reconstr Aesthet Surg 63:1209–1216

    Article  PubMed  Google Scholar 

  22. Yamanaka O, Saika S, Ohnishi Y, Kim-Mitsuyama S, Kamaraju AK, Ikeda K (2007) Inhibition of p38MAP kinase suppresses fibrogenic reaction in conjunctiva in mice. Mol Vis 13:1730–1739

    PubMed  CAS  Google Scholar 

  23. Jung SA, Lee HK, Yoon JS, Kim SJ, Kim CY, Song H, Hwang KC, Lee JB, Lee JH (2007) Upregulation of TGF-β-induced tissue transglutaminase expression by PI3K-Akt pathway activation in human subconjunctival fibroblasts. Invest Ophthalmol Vis Sci 48:1952–1958

    Article  PubMed  Google Scholar 

  24. Margeli A, Kouraklis G, Theocharis S (2003) Peroxisome proliferator activated receptor-γ (PPAR-γ) ligands and angiogenesis. Angiogenesis 6:165–169

    Article  PubMed  CAS  Google Scholar 

  25. Cheng HC, Ho TC, Chen SL, Lai HY, Hong KF, Tsao YP (2008) Troglitazone suppresses transforming growth factor beta-mediated fibrogenesis in retinal pigment epithelial cells. Mol Vis 14:95–104

    PubMed  CAS  Google Scholar 

  26. Pan H, Chen J, Xu J, Chen M, Ma R (2009) Antifibrotic effect by activation of peroxisome proliferator-activated receptor-γ in corneal fibroblasts. Mol Vis 15:2279–2286

    PubMed  CAS  Google Scholar 

  27. Yamanaka O, Miyazaki K, Kitano A, Saika S, Nakajima Y, Ikeda K (2009) Suppression of injury-induced conjunctiva scarring by peroxisome proliferator-activated receptor γ gene transfer in mice. Invest Ophthalmol Vis Sci 50:187–193

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge Jianzhen Fang, Shishen Li, and Jingjia Li, at the central laboratory of 2nd Xiangya Hospital, Central South University, for their technical assistance on this study. The studies were supported by the New Century Talents project grant from the Ministry of Education of China (No. NCET-06-0677) and Hunan Natural Science Foundation (No. 5JJ30051)

Author information

Authors and Affiliations

  1. Department of Ophthalmology, 2nd Xiangya Hospital, Central South University, Hunan, Changsha, 410011, People’s Republic of China

    Xuanchu Duan, Tantai Zhao & Huihui Chen

  2. Department of Ophthalmology, People’s Hospital of Hebei Province, Hebei, Shijiazhuang, 050051, People’s Republic of China

    Fang Fan

  3. Department of Ophthalmology, 2nd People’s Hospital of YunNan Province, Yunnan, Kunming, 650000, People’s Republic of China

    Yuehua Li

  4. Heibei University of Science and Technology, Hebei, Shijiazhuang, 050000, People’s Republic of China

    Dongning Pan

Authors
  1. Fang Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuehua Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuanchu Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tantai Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dongning Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huihui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuanchu Duan.

Additional information

No financial relationship with the organization that sponsored this research exists. The authors have full control of all primary data and agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fan, F., Li, Y., Duan, X. et al. Rosiglitazone attenuates activation of human Tenon’s fibroblasts induced by transforming growth factor -β1. Graefes Arch Clin Exp Ophthalmol 250, 1213–1220 (2012). https://doi.org/10.1007/s00417-011-1903-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-011-1903-6

Keywords

Search

Navigation