Abstract
To investigate the effects of tranilast, an inhibitor of chemical mediators and fibroblast proliferation, on the expression of transforming growth factor-beta (TGF-β)-induced protein (TGFBIp) in wild-type (WT) and homozygous (HO) granular corneal dystrophy type 2 corneal fibroblasts. Cell proliferation and cytotoxicity were measured by Cell Counting Kit-8 and lactate dehydrogenase assay. Western blotting and real-time polymerase chain reaction were used to determine changes in the expression of TGFBIp and TGFBI mRNA. We determined the effects of tranilast on phosphorylated Smad2 (pSmad2) and pSmad3, wound-healing, and expression of alpha-smooth muscle actin (α-SMA), type I collagen, and integrins. High concentrations of tranilast decreased proliferation of corneal fibroblasts but did not cause elevation of lactate dehydrogenase, except at 1.0 mM tranilast. TGF-β increased the expression of TGFBIp and TGFBI mRNA in WT and HO corneal fibroblasts. Cotreatment of corneal fibroblasts with tranilast and TGF-β reduced the levels of TGFBIp and TGFBI mRNA. In addition, application of tranilast reduced pSmad2 in WT and HO corneal fibroblasts and pSmad3 in HO corneal fibroblasts, both of which were increased initially by TGF-β. Tranilast delayed wound healing and reduced the expression of α-SMA, type I collagen, and some of integrins in WT and HO corneal fibroblasts. Application of tranilast in WT and HO corneal fibroblasts inhibited the expression of TGFBIp by blocking TGF-β signaling. Thus, tranilast may be useful in delaying or preventing the recurrence of corneal opacity in TGFBI-linked corneal dystrophies if clinical studies confirm these findings.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.