title: Activation of JNK signaling mediates connective tissue growth factor expression and scar formation in corneal wound healing.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Shi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fu-Shin X
authors.initials: FS
authors.lastname: Yu
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002461:Cell Line, Transformed; D002921:Cicatrix / Q000201:enzymology / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D003319:Corneal Stroma / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D015807:Eye Injuries, Penetrating / Q000201:enzymology / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019098:Telomerase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000873:Anthracenes; D024042:Collagen Type I; D005353:Fibronectins; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D019098:Telomerase; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one