Xu Qihe, Lucio-Cazana Javier, Kitamura Masanori, Ruan Xiongzhong, Fine Leon G, Norman Jill T
Department of Medicine, Royal Free and University College Medical School, University College London, London, UK.
Kidney Int. 2004 Dec;66(6):2119-31. doi: 10.1111/j.1523-1755.2004.66002.x.
Retinoids, a family of vitamin A metabolites or analogs, play an important role in regulating cell proliferation, differentiation, and apoptosis.
The biological importance of retinoids in the kidney and the potential of retinoids in the treatment of renal diseases are reviewed.
Vitamin A deficiency and mutations of retinoid nuclear receptors cause abnormalities in fetal kidneys, which might predispose to adult diseases such as hypertension. Further, the therapeutic value of retinoids in animal models of kidney diseases, such as lupus nephritis, puromycin aminonucleoside nephrosis, anti-glomerular basement membrane nephritis, mesangioproliferative nephritis, and acute renal allograft rejection has been unveiled recently. Retinoids target mesangial cells, podocytes, tubular epithelial cells, interstitial fibroblasts, as well as lymphocytes and macrophages. The anti-inflammation, anti-coagulation effects, and the proliferation- and immunity-modulating actions of retinoids, have been widely appreciated. Our recent in vitro data revealed a direct antifibrotic effect and a cytoprotective effect of retinoids in various renal cell types. In animal studies, the adverse effects of retinoids are generally minimal; however, the clinical use of retinoids in other diseases points to some major side effects. In addition, in vitro, retinoids can induce lipid accumulation in smooth muscle cells and macrophages and increase expression of some proinflammatory molecules, indicating that their clinical toxicity profile in the setting of renal diseases needs to be better understood.
Retinoids not only are important in renal development, but also show promise as a new generation of renal medication and deserve to be tested in clinical trials to clarify their full potential.
类视黄醇是维生素A代谢产物或类似物家族，在调节细胞增殖、分化和凋亡中发挥重要作用。
综述类视黄醇在肾脏中的生物学重要性及其在肾脏疾病治疗中的潜力。
维生素A缺乏和类视黄醇核受体突变会导致胎儿肾脏异常，这可能易引发成人疾病，如高血压。此外，类视黄醇在肾脏疾病动物模型中的治疗价值，如狼疮性肾炎、嘌呤霉素氨基核苷肾病、抗肾小球基底膜肾炎、系膜增生性肾炎和急性肾移植排斥反应，最近已被揭示。类视黄醇作用于系膜细胞、足细胞、肾小管上皮细胞、间质成纤维细胞以及淋巴细胞和巨噬细胞。类视黄醇的抗炎、抗凝作用以及增殖和免疫调节作用已得到广泛认可。我们最近的体外数据显示，类视黄醇在各种肾细胞类型中具有直接的抗纤维化作用和细胞保护作用。在动物研究中，类视黄醇的不良反应通常很小；然而，类视黄醇在其他疾病中的临床应用表明存在一些主要副作用。此外，在体外，类视黄醇可诱导平滑肌细胞和巨噬细胞中的脂质积累，并增加一些促炎分子的表达，这表明需要更好地了解它们在肾脏疾病中的临床毒性特征。
类视黄醇不仅在肾脏发育中很重要，而且作为新一代肾脏药物也显示出前景，值得在临床试验中进行测试以阐明其全部潜力。
