The beneficial role of retinoids in glomerular disease.
The beneficial role of retinoids in glomerular disease.
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DOI：
10.3389/fmed.2015.00016
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发表时间：
2015
影响因子：
3.9
通讯作者：
He JC
中科院分区：
文献类型：
--
作者：
Mallipattu SK;He JC
CKD的主要病因是最初的肾小球功能障碍和损伤的直接后果，肾小球是主要的滤过系统。足细胞是肾小球中终末分化的上皮细胞，其主要功能是维持肾滤过屏障。足细胞损伤与许多肾小球疾病有关，包括局灶性节段性肾小球硬化和HIV相关性肾病。在这些疾病中的许多情况下，足细胞可以经历去分化和增殖、凋亡或细胞分离。无论最初的损伤类型如何，足细胞最终都会失去维持肾小球滤过屏障的功能。严重的损伤会导致足细胞的丧失和肾滤过屏障的无法维持，从而导致进展性肾脏疾病。因此，预防足细胞损伤并促进其再生的治疗方法将对肾小球疾病产生重大的临床影响。维甲酸(RA)是维生素A的衍生物，具有多种细胞功能，包括诱导细胞分化、调节细胞凋亡、抑制炎症和增殖等。RA是肾脏发育所必需的，在足细胞损伤的背景下对细胞分化也是必不可少的。RA引导其有益作用的机制是多因素的，从其抗炎和抗纤维化作用到上调足细胞中足细胞分化标志物的直接作用。这篇综述的重点是提供RA在肾脏发育和肾小球疾病中的概述。我们还强调了RA恢复足细胞分化标志物和改善肾小球疾病的关键机制(S)。
The primary etiology of CKD is a direct consequence of initial dysfunction and injury of the glomerulus, the main filtration system. Podocytes are terminally differentiated epithelial cells in the glomerulus, whose major function is the maintenance of this renal filtration barrier. Podocyte injury is implicated in many glomerular diseases including focal segmental glomerular sclerosis and HIV-associated nephropathy. In many of these diseased conditions, the podocyte can either undergo dedifferentiation and proliferation, apoptosis, or cell detachment. Regardless of the initial type of injury, the podocyte ultimately loses its functional capacity to maintain the glomerular filtration barrier. Significant injury resulting in a loss of the podocytes and failure to maintain the renal filtration barrier contributes to progressive kidney disease. Consequently, therapies that prevent podocyte injury and promote their regeneration will have a major clinical impact on glomerular disease. Retinoic acid (RA), which is a derivative of vitamin A, has many cellular functions including induction of cell differentiation, regulation of apoptosis, and inhibition of inflammation and proliferation. RA is required for kidney development and is essential for cellular differentiation in the setting of podocyte injury. The mechanism by which RA directs its beneficial effects is multifactorial, ranging from its anti-inflammatory and anti-fibrotic effects to a direct effect of upregulating podocyte differentiation markers in the podocyte. The focus of this review is to provide an overview of RA in kidney development and glomerular disease. We also highlight the key mechanism(s) by which RA restores podocyte differentiation markers and ameliorates glomerular disease.