Our information showed that inhibition of JNK by SP600125 suppressed expression of CTGF, fibronectin and collagen I in response to TGF b1 stimulation, whereas inhibition of p38 by SB203580 only resulted in suppression of TGF b1 induced fibronectin expression. On the other hand, inhibition of ERK by PD98059 did not significantly alter expression of CTGF, fibronectin or collagen I in response to TGF b1 . CTGF is a secreted protein. We also measured the concentrations of CTGF in cell culture supernatants. Our data showed that TGF b1 drastically enhanced CTGF secretions and SP600125 markedly inhibited TGF b1 stimulated CTGF secretion. Nonetheless, SB203580 or PD98059 had no result on the secretion of CTGF induced by TGF b1 . These findings indicate that JNK can be a primary pathway in modulating the signals through which TGF b1 promotes CTGF, fibronectin and collagen I expression in corneal fibroblasts.
Earlier research demonstrated that inhibition of JNK can correctly inhibit TGF b1 induced CTGF expression in corneal fibroblasts . The present success concur with all the prior report and broaden the findings by demonstrating that p38 and i thought about this ERK will not be required for CTGF induction by TGF b1. Our group previously demonstrated that TGF b1 and CTGF have been upregulated dramatically in corneal stroma while in corneal wound healing, CTGF expression decreased radically in group that wounded eyes had been injected with TGF b1 antibody subconjunctivaly. TGF b1 neutralizing antibody might possibly inhibit the biological functions of TGF b1. Consequently, we indicated that TGF b1 could induce CTGF expression in vivo.
To further investigate the function of JNK in mediating CTGF expression and corneal scarring in vivo, a penetrating corneal wound model was produced and JNK was inhibited with subconjunctival injection of SP600125. Immunofluorescence effects showed that there was small expression of p JNK in corneas of usual rat, but p JNK expression was considerably improved from the corneal stroma ATP-competitive ROCK inhibitor just after penetrating corneal wound. Subconjunctival injection of SP600125 could inhibite p JNK expression compared with handle group obtained physiological saline remedy . This indicated that subconjunctival injection of SP600125 could significantly inhibit activation of JNK induced by corneal wounding. It had been also located that expression of TGF b1 mRNA, CTGF mRNA and protein markedly improved in corneal stroma following damage.
Subconjunctival injection of SP600125 could plainly inhibit CTGF mRNA and protein expression, but didn’t influence TGF b1 mRNA expression . These effects suggest that inhibition of JNK with subconjunctival injection of SP600125 could inhibit CTGF expression in corneal wound healing.