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.
Chang
Y
Y
Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan City, China.
Wu
X-Y
XY
D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002921:Cicatrix / Q000201:enzymology* / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D003315:Cornea / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000873:Anthracenes; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; C432165:pyrazolanthrone; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8