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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)
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.
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.
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.
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.
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