Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone
Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone
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DOI：
10.1152/ajpendo.00370.2004
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发表时间：
2005-06-01
影响因子：
5.1
通讯作者：
Nakajima, A
中科院分区：
文献类型：
--
作者：
Iwasaki, T;Mukasa, K;Nakajima, A
脱氢表雄酮（DHEA）是一种肾上腺类固醇。血清中DHEA及其硫酸盐（DHEA-S）的浓度在25岁至30岁之间达到峰值，此后稳步下降。据报道，人体DHEA-S浓度与心血管疾病死亡呈负相关。在这项研究中，我们研究了 DHEA 对培养的心脏成纤维细胞中胶原蛋白 mRNA 和胶原蛋白合成的调节作用。与对照组相比，DHEA (10(-6) M) 处理导致 I 型前胶原 mRNA 表达显着降低。这伴随着培养基中I型原胶原蛋白积累的显着减少以及细胞基质中I型原胶原蛋白合成的显着减少。此外，为了证实体外结果，我们给 Sprague-Dawley 大鼠注射 DHEA，并用血管紧张素 II 治疗 8 周以诱导心脏损伤。 DHEA 处理的大鼠心脏中 I 型原胶原 mRNA 表达显着降低，心脏纤维化显着受到抑制，且收缩压不降低。这些结果有力地表明，DHEA 可以在体内和体外转录水平上直接减弱心脏成纤维细胞中 I 型胶原蛋白的合成。
Dehydroepiandrosterone (DHEA) is a type of adrenal steroid. The concentrations of DHEA and its sulfate (DHEA-S) in serum reach a peak between the ages of 25 and 30 yr and thereafter decline steadily. It was reported that DHEA-S concentration in humans is inversely related to death from cardiovascular diseases. In this study, we examined the effects of DHEA on regulation of collagen mRNA and collagen synthesis in cultured cardiac fibroblasts. Treatment with DHEA (10(-6) M) resulted in a significant decrease in procollagen type I mRNA expression compared with controls. This was accompanied by a significant decrease in procollagen type I protein accumulation in the medium and also a significant decrease in procollagen type I protein synthesis in the cellular matrix. Furthermore, to confirm in vitro results, we administered DHEA to Sprague-Dawley rats, which were treated with angiotensin II for 8 wk to induce cardiac damage. Procollagen type I mRNA expression was significantly decreased and cardiac fibrosis significantly inhibited in DHEA-treated rat hearts without lowering the systolic blood pressure. These results strongly indicate that DHEA can directly attenuate collagen type I synthesis at the transcriptional level in vivo and in vitro in cardiac fibroblasts.