Activation of JNK Signaling Mediates Connective Tissue Growth Factor Expression and Scar Formation in Corneal Wound Healing

• Published in: PloS one Vol. 7; no. 2; p. e32128
• Main Authors: Shi, Long, Chang, Yuan, Yang, Yongmei, Zhang, Ying, Yu, Fu-Shin X., Wu, Xinyi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.02.2012; Public Library of Science (PLoS)
• Subjects: Acanthamoeba; Analysis; Animals; Anthracenes - pharmacology; Biology; Bone morphogenetic proteins; c-Jun protein; Cell adhesion & migration; Cell Line, Transformed; Cicatrix - enzymology; Cicatrix - pathology; Collagen; Collagen (type I); Collagen Type I - metabolism; Connective tissue growth factor; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; Connective Tissue Growth Factor - secretion; Connective tissues; Cornea; Cornea - drug effects; Cornea - enzymology; Cornea - pathology; Corneal Stroma - drug effects; Corneal Stroma - enzymology; Corneal Stroma - pathology; Enzyme Activation - drug effects; Eye Injuries, Penetrating - enzymology; Eye Injuries, Penetrating - pathology; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - pathology; Fibronectin; Fibronectins; Fibronectins - metabolism; Flavonoids - pharmacology; Fusarium; Gene Expression Regulation - drug effects; Growth factors; Humans; Imidazoles - pharmacology; Inhibitors; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; Male; MAP kinase; MAP Kinase Signaling System - drug effects; Medicine; Pathogenesis; Phosphorylation; Phosphorylation - drug effects; Proteins; Pyridines - pharmacology; Rats; Rats, Wistar; Scars; Science Policy; Signal transduction; Signaling; Smooth muscle; Stroma; Telomerase; Telomerase - metabolism; Transcription factors; Transforming growth factor; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; Transforming growth factors; Wound care; Wound healing; Wound Healing - drug effects; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032128

Connective Tissue Growth Factor (CTGF) and Transforming growth factor-β1 (TGF-β1) are key growth factors in regulating corneal scarring. Although CTGF was induced by TGF-β1 and mediated many of fibroproliferative effects of TGF-β1, 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-β1 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-β1 activated MAPK pathways in THSF cells. JNK inhibitor significantly inhibited CTGF, fibronectin and collagen I expression induced by TGF-β1 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 for corneal scarring.