Dexamethasone is a novel potent inducer of connective tissue growth factor expression. Implications for glucocorticoid therapy.
Due to its potent effect on fibroblast proliferation and extracellular matrix deposition, connective tissue growth factor (CTGF) seems to play an important role in the pathogenesis of fibrotic disease. Since glucocorticoids are frequently used for the therapy of these disorders, we determined a potential effect of these steroids on CTGF expression. In cultured fibroblasts, a striking induction of CTGF expression was observed after dexamethasone treatment and occurred in a time- and dose-dependent manner. This effect was obviously not mediated by the CTGF inducer transforming growth factor-beta1, since expression of this factor was down-regulated by the glucocorticoid. Most importantly, CTGF expression levels also increased substantially in various tissues and organs by systemic glucocorticoid treatment of mice. After cutaneous injury, a strong induction of CTGF expression was seen in the wounds of nontreated mice. However, no further increase in the levels of CTGF mRNA occurred in wounded skin compared with unwounded skin of glucocorticoid-treated animals, suggesting the presence of other factors in the wound that might compensate for the effect of the steroids. Tumor necrosis factor-alpha was identified as a possible mediator of this effect because this factor suppressed CTGF expression in cultured fibroblasts and also blocked the glucocorticoid-induced CTGF production by these cells. These findings indicate that glucocorticoids stimulate CTGF expression in normal tissues and organs but not in highly inflamed areas.
Dammeier
J
J
Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried, Germany.
Beer
H D
HD
Brauchle
M
M
Werner
S
S
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D055513:Connective Tissue Growth Factor; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
C526318:CCN2 protein, mouse; D002352:Carrier Proteins; D005938:Glucocorticoids; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D003907:Dexamethasone