May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Smad Signal Transduction Pathway in Transforming Growth Factor 1 on Inducing the Human Tenon’s Fibroblasts to Myofibroblasts
Author Affiliations & Notes
  • Y. Xiao
    Department of Ophthalmology, Huashan Hospital, Shanghai, China
  • W. Ye
    Department of Ophthalmology, Huashan Hospital, Shanghai, China
  • G.-T. Xu
    Laboratory of Clinical Visual, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai JiaoTong University School of Medicine, Shanghai, China
  • Footnotes
    Commercial Relationships Y. Xiao, None; W. Ye, None; G. Xu, None.
  • Footnotes
    Support stcsm grant 04JC14023
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5668. doi:
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      Y. Xiao, W. Ye, G.-T. Xu; Smad Signal Transduction Pathway in Transforming Growth Factor 1 on Inducing the Human Tenon’s Fibroblasts to Myofibroblasts. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5668.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: To assess the role of SMAD pathway in TGF-ß1-induced human tenon’s fibroblasts (HTFs) transdifferentiation into myofibroblasts and to identify the potential pharmacologic target for the inhibition of scar formation after glaucoma surgery.

Methods:: HTFs were obtained from patients with cataract during surgery. They were induced by 10µg/L TGF-ß1. TGF-ß1-induced expression of p-Smad2 was determined by Western blot analysis. TGF-ß-induced mRNA expressions of alpha smooth muscle actin (α-SMA, a marker of myofibroblast) and connective tissue growth factor (CTGF, the potent mediator of transdifferentiation) were analyzed by RT-PCR. The protein expressions of α-SMA and CTGF were determined by Western blot analysis and immunocytochemistry. A specific pharmacologic kinase inhibitor was used to confirm the involvement of SMAD-dependent pathways.

Results:: The increased expressions of p-Smad2 were first observed when the cells were incubated with TGF-ß for 5 min, which lasted up to 24 hours. There were two peaks of the elevated expression, at 1 hour and 12 hours, respectively. The relative mRNA expression of CTGF was up-regulated, with a peak at 12 hours after TGF-ß simulation. The relative mRNA expression of α-SMA was also increased, with the peak at 24 hours after TGF-ß simulation. The protein changes of CTGF and α-SMA demonstrated the same pattern of the changes in mRNA expression. The peaks for CTGF and α-SMA were at 24 and 48 hours respectively. SMAD inhibitor prevented the up-regulations of CTGF and α-SMA, at both protein and RNA levels.

Conclusions:: SMAD pathway plays an important role in TGF-ß-induced HTFs transdifferentiation into myofibroblasts. SMAD inhibitor could abrogate TGF-ß1-induced fibroblast transdifferentiation, and thus, seems to be able to inhibit the scar formation after glaucoma surgery.

Keywords: signal transduction • wound healing 
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