摘要
背景:肾小球毛细血管内衬高度专业化的内皮细胞,主要负责调节流体和小溶质的高通量过滤。在滤过程中,血浆在到达狭缝隔膜(一种连接相邻足细胞的特殊类型的细胞间连接处)之前,穿过有窗的内皮和基底膜。方法:对肾小球滤过屏障组分(如肾小球内皮细胞、足细胞、肾小球基底膜)及糖尿病对肾小球滤过屏障结构的影响进行PubMed检索。结果与结论:许多糖尿病患者肾功能不全的发病特点是蛋白尿/蛋白尿,这是一种由多种因素触发的病理生理事件:(1)内皮细胞活化和糖基萼的遮挡,(2)内皮细胞功能丧失,(2)足细胞通过清道夫受体重新摄取白蛋白,(4)足细胞骨架的重排。然而,由于足细胞渗出并不总是导致蛋白尿,肾小球滤过屏障的所有成分(包括足细胞、内皮细胞和基底膜)之间的动态相互作用可能是正常人有效滤过的基础。因此,设想了足细胞、内皮细胞和基底膜在肾小球功能稳态中的相互作用。虽然这种相互作用的确切性质仍有待澄清,但有可能是:(一)肾小球内皮细胞与足细胞之间的相互作用,(二)肾小球内皮细胞与肾小球基底膜的相互作用,(三)足细胞与肾小球基底膜的相互作用,以及(四)这三种成分的同时相互作用共同支持健康个体的有效滤过。对这些不同的相互作用的全面理解仍然难以理解。阐明这些多方面的相互作用将为更好地理解肾功能障碍的病理生理学奠定基础。
关键词: 肾小球滤过屏障,内皮,糖尿病,足细胞,肾小球基底膜,肾功能不全。
Current Medicinal Chemistry
Title:Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in Diabetes: Are the Gaps Still Illusive?
Volume: 25 Issue: 13
关键词: 肾小球滤过屏障,内皮,糖尿病,足细胞,肾小球基底膜,肾功能不全。
摘要: Background: Glomerular capillaries are lined with highly specialized fenestrated endothelium which are primarily responsible to regulate high flux filtration of fluid and small solutes. During filtration, plasma passes through the fenestrated endothelium and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocytes.
Methods: A PubMed search was done for recent articles on components of the glomerular filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement membrane, and the effect of diabetes on these structures.
Results and Conclusion: Generally, the onset of kidney dysfunction in many diabetic patients is characterized by albuminuria/proteinuria, a pathophysiological event triggered by several factors including; (i) endothelial activation and shading of glycocalyx, (ii) loss of endothelial cell function, (ii) re-uptake of albumin by podocyte through a scavenger receptors and (iv) rearrangement of podocyte cytoskeleton. Howeover, as podocyte effacement does not always lead to proteinuria, the dynamic interplay between all constituents of the glomerular filtration barrier including podocytes, endothelial cells and the basement membrane may be fundamental for the effective filtration in healthy individuals. Thus, a putative cross-talk amongst podocytes, endothelial cells and the basement membrane in the homeostasis of glomerular function is envisaged. Although, the exact nature of this cross-talk remains to be clearly elucidated, it is possible that the interaction between: (i) glomerular endothelial cells and podocytes, (ii) glomerular endothelial cells and glomerular basement membrane, (iii) podocytes and glomerular basement membrane, and (iv) the simultaneous interaction amongst the three components collectively underpin effective filtration in healthy individuals. A comprehensive understanding of these different interactions still remains elusive. The elucidation of these multifaceted interactions will set the stage for greater understanding of the pathophysiology of kidney dysfunction.
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Cite this article as:
Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in Diabetes: Are the Gaps Still Illusive?, Current Medicinal Chemistry 2018; 25 (13) . https://dx.doi.org/10.2174/0929867324666170705124647
DOI https://dx.doi.org/10.2174/0929867324666170705124647 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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