GSK3B/β-catenin/TCF通路介导Pirfenidone调控人眼Tenon's囊成纤维细胞周期的机制研究

人Tenon's囊成纤维细胞过度增殖是青光眼手术滤过区过度瘢痕化主要原因。研究表明Pirfenidone能有效阻滞人Tenon's囊成纤维细胞于G1期，GSK3B/β-catenin/TCF信号通路是调控细胞生存的重要通路，对Pirfenidone抑制TGF-β/Smad有调控作用。已发现GSK3B在人Tenon's囊成纤维细胞广泛表达，而GSK3B通路活性增强可阻遏人Tenon's囊成纤维细胞周期，提示Pirfenidone可能通过GSK3B/β-catenin/TCF通路进行细胞周期调控。本课题拟明确：GSK3B//β-catenin/TCF通路介导的Pirfenidone在人Tenon's囊成纤维细胞的作用及具体调控机制。本研究将为青光眼术后滤过区瘢痕化调控提供新的思路和治疗靶点。

Abstract: The Excessive proliferation of Human Tenon's capsule fibroblasts(HTFs) is the direct and major cause of the scarring which always appear after glaucoma surgery. Studies have shown that Pirfenidone(PFD) can effectively block the cell proliferation cycle of HTFs and keep them stay in G1 phase with an unknown mechanism. GSK3B/β-catenin/TCF signaling pathways is a major pathway that regulate cell survival and does an important role on the inhibition of PFD to TGF-β/Smad. GSK3B widely expressed in HTFs and the increased activity of GSK3B pathways weakened the cell proliferation cycle of HTFs and indicated that PFD may regulate the cell proliferation cycle though GSK3B/β-catenin/TCF pathway. Our research intend to clarify the mechanism of the effect and regulation of PFD to the cell proliferation cycle of HTFs though GSK3B/β-catenin/TCF pathway. Our research will provide new ideas and therapeutic targets to the scarring after glaucoma surgery.