JNK1/2 siRNA inhibits transforming-growth factor-beta1-induced connective tissue growth factor expression and fibrotic function in THSFs.

Transforming-growth factor-beta1 (TGF-beta1) plays an important role in fibrosis by inducing connective tissue growth factor (CTGF) expression. In cornea, however, signaling pathway in the process is unclear. In this paper, real-time RT-PCR and Western blot analysis were used to examine the expression and TGF-beta1-induced upregulation of CTGF in telomerase-immortalized human cornea stroma fibroblast cells (THSFs). A detailed molecular mechanism for TGF-beta1-mediated cell proliferation and collagen I production was then investigated by detecting the activation of JNK pathway in TGF-beta1-stimulated THSFs and blocking the JNK pathway using JNK1/2 siRNA. Both TGF-beta1 and CTGF clearly induced cell proliferation in THSFs which was inhibited by functional blocking CTGF by anti-CTGF antibody. Blocking JNK pathway by JNK1/2 siRNA significantly inhibited induction of CTGF by TGF-beta1. Taken together, the data indicate that CTGF is critical to the fibrosis process in wounded human cornea, acting via upregulation and activation of JNK signaling pathway.