Dimke Henrik, Maezawa Yoshiro, Quaggin Susan E
aDepartment of Cardiovascular and Renal Research, Institute of Molecular medicine, University of Southern Denmark, Odense, Denmark bDepartment of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine cDivision of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan dFeinberg Cardiovascular Research Institute and Division of Nephrology and Hypertension, Northwestern University, Chicago, Illinois, USA.
Curr Opin Nephrol Hypertens. 2015 May;24(3):231-8. doi: 10.1097/MNH.0000000000000117.
The glomerulus is a unique structure required for filtration of blood, while retaining plasma proteins based on size and charge selectivity. Distinct cell types form the structural unit that creates the filtration barrier. Structurally, fenestrated endothelial cells line the capillary loops and lie in close contact with mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and separated from the endothelial compartment by the glomerular basement membrane. In order for this highly specialized structure to function, cross-communication between these cells must occur.
Although classical studies have established key roles for vascular endothelial and platelet-derived growth factors in glomerular cross-communication, novel paracrine signaling pathways within the glomerulus have recently been identified. In addition, unique cellular pathways of established signaling cascades have been identified that are important for maintaining glomerular barrier function in health and disease.
Here, we will review our current understanding of the processes of cross-communication between the unique cellular constituents forming the glomerular filtration unit. We will highlight recent findings of cellular crosstalk via signaling pathways that regulate glomerular barrier function in pathophysiological conditions.
肾小球是血液滤过所需的独特结构,基于大小和电荷选择性保留血浆蛋白。不同的细胞类型构成了形成滤过屏障的结构单元。在结构上,有窗孔的内皮细胞排列在毛细血管袢内,并与系膜细胞紧密接触。足细胞通过称为裂孔隔膜的特殊细胞间连接相连,并通过肾小球基底膜与内皮腔分隔开。为了使这种高度专业化的结构发挥功能,这些细胞之间必须发生相互交流。
尽管经典研究已确定血管内皮生长因子和血小板衍生生长因子在肾小球相互交流中起关键作用,但最近已在肾小球内发现了新的旁分泌信号通路。此外,已确定了既定信号级联反应的独特细胞途径,这些途径对于在健康和疾病状态下维持肾小球屏障功能很重要。
在此,我们将综述目前对构成肾小球滤过单位的独特细胞成分之间相互交流过程的理解。我们将重点介绍通过调节病理生理条件下肾小球屏障功能的信号通路进行细胞间相互作用的最新发现。