The role of c-Jun N-terminal kinases 1/2 in transforming growth factor beta(1)-induced expression of connective tissue growth factor and scar formation in the cornea.

Transforming growth factor beta(1) (TGF-beta(1)) plays an important role in corneal scar formation, mediated by connective tissue growth factor (CTGF). This study was designed to investigate the effect of c-Jun N-terminal kinase (JNK) 1 and 2 on TGF-beta(1)-regulated CTGF gene expression and corneal scar formation in telomerase-immortalized human corneal stroma fibroblast (THSF) cells. The effects of CTGF, TGF-beta(1) and a JNK inhibitor (SP600125) on the proliferation of THSF cells were studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Both CTGF and TGF-beta(1) increased THSF cell proliferation and SP600125 inhibited this effect. Immunofluorescence analysis showed that TGF-beta(1) stimulated the activation of JNK1/2 and induced cell migration, effects that were inhibited by SP600125. Analysis by real-time reverse transcription-polymerase chain reaction showed that the mRNA levels of the genes for CTGF, fibronectin and collagen Ialpha(1) in wound and corneal scar formation were reduced by SP600125 pre-treatment.