Dexamethasone Is a Novel Potent Inducer of Connective Tissue Growth Factor Expression

Abstract

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 dosedependent manner. This effect was obviously not mediated by the CTGF inducer transforming growth factor-␤1, 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-␣ 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.

Expression and regulation of osteopontin and connective tissue growth factor transcripts in rat anterior pituitary

“…Among the hormones tested, only dexamethasone significantly increased CTGF transcript levels after long-term treatment and even more impressively within 5 h after a single injection of this steroid (data not shown). A rapid and dramatic induction of CTGF mRNA and protein by dexamethasone has also been observed in cultured fibroblasts and described recently (Dammeier et al 1998). The same authors also reported on dexamethasone induced upregulation of CTGF mRNA levels in heart, kidney and skin of mice that had been injected repeatedly with dexamethasone.…”

Expression of the angiomatrix and angiogenic proteins CYR61, CTGF, and VEGF in osteonecrosis of the femoral head

“…In a study in mice CTGF expression was induced by corticosteroids in fibroblasts. 45 In our study, we did not see an increased CTGF expression in corticosteroid-related ON compared to ON due to other causes. However, this could be explained by the time difference of bone cylinder retrieval and corticosteroid therapy.…”

Connective Tissue Growth Factor Expression in the Rat Remnant Kidney Model and Association with Tubular Epithelial Cells Undergoing Transdifferentiation

“…A unique, specific TGF-␤ response element has been identified in the CTGF promoter that directly induces transcriptional activation of the gene, 17 but expression may also be induced by corticosteroids. 8 CTGF has mitogenic action on fibroblasts 12,22 and can induce the extracellular matrix-associated genes type I colla- gen, fibronectin, and ␣5-integrin. [10][11][12] It modulates cell adhesion in fibroblasts and affects neovascularization.…”