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.
Chang
Yuan
Y
Department of Ophthalmology, Qilu Hospital of Shandong University, No. 107, Wenhua Road (West), Lixia District, 250012 Jinan, Shandong, China.
Wu
Xin-Yi
XY
D049109:Cell Proliferation; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8