Aldosterone-induced fibrosis in the kidney: questions and controversies.
Aldosterone-induced fibrosis in the kidney: questions and controversies.
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DOI：
10.1053/j.ajkd.2011.03.029
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Gong R
中科院分区：
文献类型：
--
作者：
Brem AS;Morris DJ;Gong R
多年来，醛固酮因其在维持体液中的作用而一直是肾脏生理学家最喜欢的话题。研究人员直到最近才认识到这种激素的第二种促炎和促纤维化作用。盐皮质激素与醛固酮一样，会引发促纤维化过程，该过程在许多方面模仿伤口愈合的早期阶段。根据所涉及的细胞类型，醛固酮可能通过经典盐皮质激素受体 (MR)、非经典膜相关 MR 和/或糖皮质激素受体激活促纤维化过程。在肾脏中，醛固酮的作用可被 11β-羟基类固醇脱氢酶异构体（11β-HSD-1 和 11β-HSD-2）产生的内源性糖皮质激素的 11-脱氢代谢物减弱。因此，肾 11β-HSD 亚型可能有两种功能：防止内源性糖皮质激素不适当地结合并激活 MR，并合成限制醛固酮作用的药物。虽然饮食中的钠与加重醛固酮诱导的肾纤维化过程有关，但初步研究结果与以下观点一致：即使在没有主动钠转运的情况下，单独的醛固酮也可以启动肾组织中的基质产生。因此，越来越多的实验室和临床证据支持在患有肾小球和肾小管疾病的患者中使用醛固酮作用抑制剂。
Over the years, aldosterone has been a favorite topic of renal physiologists given its role in the maintenance of the body fluids. Investigators are only recently coming to appreciate a second pro-inflammatory and pro-fibrotic role for this hormone. Mineralocorticoids, like aldosterone, trigger a pro-fibrotic process, which in many respects mimics the early phase of wound healing. Depending on the type of cell involved, aldosterone may activate the pro-fibrotic process through classical mineralocorticoid receptors (MR), non-classical membrane associated MR, and/or glucocorticoid receptors. In the kidney, the actions of aldosterone can be attenuated by 11-dehydro metabolites of endogenous glucocorticoids generated by isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD-1 and 11β-HSD-2). Thus the renal 11β-HSD isoforms may have two functions; to prevent endogenous glucocorticoids from inappropriately binding to and activating MR and to synthesize agents that limit the actions of aldosterone. While sodium in the diet has been implicated in aggravating aldosterone induced renal fibrotic processes, preliminary findings are consistent with the view that aldosterone alone can initiate the matrix production in renal tissue even in the absence of active sodium transport. Thus, there is a growing body of laboratory and clinical evidence supporting the use of inhibitors of aldosterone action in patients with both glomerular and tubular diseases.