activation of jnk signaling mediates connective tissue growth factor expression and scar formation in corneal wound healing物信号介导的激活结缔组织生长因子表达和角膜伤口愈合的疤痕形成.pdfVIP

Activation of JNK Signaling Mediates Connective Tissue Growth Factor Expression and Scar Formation in Corneal Wound Healing 1. 1. 1 1 2 1 Long Shi , Yuan Chang , Yongmei Yang , Ying Zhang , Fu-Shin X. Yu , Xinyi Wu * 1 Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China, 2 Departments of Ophthalmology, Anatomy, and Cell Biology, Wayne State University School of Medicine, Detroit, United States of America Abstract Connective Tissue Growth Factor (CTGF) and Transforming growth factor-b1 (TGF-b1) are key growth factors in regulating corneal scarring. Although CTGF was induced by TGF-b1 and mediated many of fibroproliferative effects of TGF-b1, the signaling pathway for CTGF production in corneal scarring remains to be clarified. In the present study, we firstly investigated the effects of c-Jun N-terminal kinase (JNK) on CTGF expression induce by TGF-b1 in Telomerase-immortalized human cornea stroma fibroblasts (THSF). Then, we created penetrating corneal wound model and determined the effect of JNK in the pathogenesis of corneal scarring. TGF- b1 activated MAPK pathways in THSF cells. JNK inhibitor significantly inhibited CTGF, fibronectin and collagen I expression induced by TGF-b1 in THSF. In corneal wound healing, the JNK inhibitor significantly inhibited CTGF expression, markedly improved the architecture of corneal stroma and reduced corneal scar formation, but did not have a measurable impact on corneal wound healing in vivo. Our results indicate that JNK mediates the expression of CTGF and corneal scarring in corneal wound healing, and might be considered as specific targets of drug therapy fo