REGULATION OF THE EXPRESSION OF TISSUE INHIBITOR OF METALLOPROTEINASES AND COLLAGENASE BY RETINOIDS AND GLUCOCORTICOIDS IN HUMAN-FIBROBLASTS
REGULATION OF THE EXPRESSION OF TISSUE INHIBITOR OF METALLOPROTEINASES AND COLLAGENASE BY RETINOIDS AND GLUCOCORTICOIDS IN HUMAN-FIBROBLASTS
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DOI：
10.1172/jci113203
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发表时间：
1987-11-01
影响因子：
15.9
通讯作者：
WELGUS, HG
中科院分区：
文献类型：
--
作者：
CLARK, SD;KOBAYASHI, DK;WELGUS, HG
观察维甲酸类化合物和糖皮质激素对间质胶原酶和金属蛋白酶组织抑制因子(TIMP)表达的影响。有效的维甲酸诱导apprx的TIMP的产生呈剂量依赖性的特异性增加。单层培养来自不同组织的人成纤维细胞两到三倍，同时导致胶原酶分泌类似程度的下降。这些作用在培养8-12h后即可显现，并在停用维甲酸化合物后的24h内消失。维甲酸对TIMP产生的影响是通过增加新的抑制蛋白的生物合成来实现的。类似地，TIMP信使RNA(MRNA)的稳态水平增加伴随着胶原酶mRNA的减少，这表明视黄醇的作用在转录上受到控制。这些数据表明，维甲酸共同调节胶原酶和TIMP的表达，并以相反的方式进行。地塞米松引起胶原酶产量的剂量依赖性、特异性降低，但不改变TIMP的生物合成。这些发现与胶原酶mRNA的显著降低相平行，而TIMP mRNA没有任何伴随的变化。因此，TIMP和胶原酶的表达似乎独立地受到糖皮质激素的调节。
The regulation of the expression of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP) was examined in response to both retinoid compounds and glucocorticoids. Effective retinoids induced a dose-dependent, specific increase in the production of TIMP of .apprx. two- to threefold by monolayer cultures of human fibroblasts derived from various tissues, while simultaneously causing a decrease in collagenase secretion of similar magnitude. These effects were apparent by 8-12 h in culture and disappeared within 24 h after the withdrawal of retinoid compounds. The retinoid effect on TIMP production was mediated via an increased biosynthesis of new inhibitor protein. Similarly, increased steady state levels of TIMP messenger RNA (mRNA) accompanied by decreased quantities of collagenase mRNA were demonstrated, suggesting transcriptional control of the retinoid action. The data suggest that retinoids co-regulate the expression of collagenase and TIMP, and do so in an inverse manner. Dexamethasone caused a dose-dependent, specific decrease in collagenase production without altering the biosynthesis of TIMP. These findings were paralleled by a marked reduction in collagenase mRNA, without any accompanying change in TIMP mRNA. Therefore, TIMP and collagenase expression appear to be independently modulated by glucocorticoids.