Dexamethasone is a novel potent inducer of connective tissue growth factor expression - Implications for glucocorticoid therapy
Dexamethasone is a novel potent inducer of connective tissue growth factor expression - Implications for glucocorticoid therapy
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DOI：
10.1074/jbc.273.29.18185
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发表时间：
1998-07-17
影响因子：
4.8
通讯作者：
Werner, S
中科院分区：
文献类型：
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作者：
Dammeier, J;Beer, HD;Werner, S
结缔组织生长因子(CTGF)由于其对成纤维细胞增殖和细胞外基质沉积的强大作用，似乎在纤维化疾病的发病机制中起着重要作用。由于糖皮质激素经常用于这些疾病的治疗，我们确定了这些类固醇对CTGF表达的潜在影响。在培养的成纤维细胞中，地塞米松显著诱导CTGF的表达，且呈时间和剂量依赖关系，这种作用明显不受CTGF诱导剂转化生长因子-β1的介导，因为该因子的表达受糖皮质激素的下调。更重要的是，全身应用糖皮质激素后，CTGF在小鼠各组织器官中的表达水平也显著升高，在皮肤损伤后，非治疗组小鼠创面CTGF表达明显增强，但创面CTGF mRNA表达水平与非创面相比没有进一步增加，提示创面存在其他可能补偿激素作用的因素。肿瘤坏死因子-α被认为可能是这一效应的媒介，因为该因子抑制了培养的成纤维细胞中CTGF的表达，并阻断了糖皮质激素诱导的这些细胞产生CTGF。这些发现表明，糖皮质激素刺激CTGF在正常组织和器官中的表达，但在高度炎症区域不刺激。
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-beta 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-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.