Möller Clemens C, Flesche Jan, Reiser Jochen
Department of Medicine, Program in Glomerular Disease and Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
J Am Soc Nephrol. 2009 May;20(5):950-3. doi: 10.1681/ASN.2008030329. Epub 2008 Sep 10.
Physiologic permeability of the glomerular capillary depends on the normal structure of podocyte foot processes forming a functioning slit diaphragm in between. Mutations in several podocyte genes as well as specific molecular pathways have been identified as the cause for progressive kidney failure with urinary protein loss. Podocyte injury is a hallmark of glomerular disease, which is generally displayed by the rearrangement of the podocyte slit diaphragm and the actin cytoskeleton. Recent studies demonstrate a unique role for the Ca(2+)-permeable ion channel protein TRPC6 as a regulator of glomerular ultrafiltration. In both genetic and acquired forms of proteinuric kidney disease, dysregulation of podocyte TRPC6 plays a pathogenic role. This article illustrates how recent findings add to emerging concepts in podocyte biology, particularly mechanosensation and signaling at the slit diaphragm.
肾小球毛细血管的生理通透性取决于足细胞足突的正常结构，足突之间形成了起作用的裂孔隔膜。已确定几种足细胞基因的突变以及特定分子途径是导致进行性肾衰竭伴尿蛋白丢失的原因。足细胞损伤是肾小球疾病的一个标志，通常表现为足细胞裂孔隔膜和肌动蛋白细胞骨架的重排。最近的研究表明，钙通透性离子通道蛋白TRPC6作为肾小球超滤的调节因子具有独特作用。在遗传性和获得性蛋白尿性肾病中，足细胞TRPC6的失调都起着致病作用。本文阐述了最近的研究结果如何丰富了足细胞生物学的新观念，尤其是裂孔隔膜处的机械感受和信号传导。
