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Yuanquan Yang, Hua Yang, Zheng Wang, Fan Zhang, Peter S. Reinach; Dependence Of Tgfβ-induced Corneal Fibrosis On Trpv1 Activation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2013.
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Previously we reported functional expression of transient receptor potential cation channel V1 (TRPV1) in cultured human corneal fibroblasts. As TRPV1 activation by severe injury in mice contributes to inappropriate healing, we determined if the presence of TRPV1 is essential for TGFβ to induce myofibroblast transdifferentiation.
Fresh human cadaver corneas were obtained from New York Upstate Transplant Service. Stromal fibroblasts were isolated and cultured following a described method. Western blot analysis probed for α-smooth muscle actin (SMA) and TRPV1 protein expression. Immunocytochemistry stained for α-SMA expression. ELISA evaluated the effects of capsaicin (CAP), a TRPV1 selective agonist, on IL-6 release.
TGF-β1 (1ng/ml) treatment for 48 h upregulated TRPV1 protein expression. Preincubation with capsazepine (CPZ, 5 µM), a selective TRPV1 antagonist, significantly reduced TGF-β1 induced α-SMA protein expression. After 24 h exposure to CAP (50 µM), IL-6 maximally rose 2.5-fold above the control level, which was blocked by either CPZ (5 µM) or SB-203580 (10 µM), a p38 mitogen-activated protein kinase (MAPK) inhibitor.
TRPV1 blockade delays and reduces TGF-β1-induced transdifferentiation of human corneal fibroblasts. TRPV1 activation induces IL-6 release through p38 MAPK pathway activation, which may also contribute to fibrosis.
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