Nonimmunologic targets of immunosuppressive agents in podocytes.
Nonimmunologic targets of immunosuppressive agents in podocytes.
复制标题
足细胞中免疫抑制剂的非免疫靶点。
DOI：
10.1016/j.krcp.2015.03.003
复制
发表时间：
2015
影响因子：
3
通讯作者：
Fornoni,Alessia
中科院分区：
文献类型：
--
作者：
Yoo,Tae-Hyun;Fornoni,Alessia
蛋白尿是肾小球疾病的特征性表现，与肾脏预后密切相关。此外，减少蛋白尿的治疗干预可改善肾脏预后。越来越多的证据表明足细胞是肾小球损伤和蛋白尿的关键调节因子。足细胞或肾小球内脏上皮细胞是高度特化和分化的细胞，其与相邻足细胞形成交叉指状足突，其通过称为“狭缝隔膜”（SD）的细胞外结构桥接在一起。SD充当血浆蛋白的大小和电荷选择性屏障。SD结构紊乱或SD相关蛋白丢失导致足细胞损伤和蛋白尿。在过去的几十年中，几种免疫调节剂已被用于治疗肾小球疾病和减少蛋白尿。有趣的是，最近的研究表明，免疫抑制剂可以对SD相关蛋白产生直接影响，并稳定足细胞中的肌动蛋白细胞骨架，因此引入了免疫调节剂肾保护的非免疫机制的概念。本文综述了免疫调节剂直接靶向足细胞的证据。
Proteinuria is a characteristic finding in glomerular diseases and is closely associated with renal outcomes. In addition, therapeutic interventions that reduce proteinuria improve renal prognosis. Accumulating evidence has demonstrated that podocytes act as key modulators of glomerular injury and proteinuria. The podocyte, or glomerular visceral epithelial cell, is a highly specialized and differentiated cell that forms interdigitated foot processes with neighboring podocytes, which are bridged together by an extracellular structure known as the “slit diaphragm” (SD). The SD acts as a size- and charge-selective barrier to plasma protein. Derangement of SD structure or loss of SD-associated protein results in podocyte injury and proteinuria. During the past decades, several immune-modulating agents have been used for the treatment of glomerular diseases and for the reduction of proteinuria. Interestingly, recent studies have demonstrated that immunosuppressive agents can have a direct effect on the SD-associated proteins and stabilize actin cytoskeleton in podocyte and have therefore introduced the concept of nonimmunologic mechanism of renoprotection by immunomodulators. This review focuses on the evidence that immuno-modulating agents directly target podocytes.