Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Semin Nephrol. 2012 Jul;32(4):342-9. doi: 10.1016/j.semnephrol.2012.06.005.
This article summarizes the basic cellular and extracellular events in the development of the glomerulus and assembly of the glomerular basement membrane (GBM), paying special attention to laminin (LM) and type IV collagen. Cellular receptors for GBM proteins, including the integrins, dystroglycan, and discoidin domain receptor 1 also are discussed. Evidence is reviewed showing that the laminin isoform present in the earliest GBM, LM-111, and final isoform found in the mature GBM, LM-521, are each derived from both endothelial cells and podocytes. Although the early collagen α1α2α1(IV) similarly derives from endothelial cells and podocytes, collagen α3α4α5(IV) found in fully mature GBM is a product solely of podocytes. Genetic diseases affecting laminin and type IV collagen synthesis also are presented, with an emphasis on mutations to LAMB2 (Pierson syndrome) and COL4A3, COL4A4, and COL4A5 (Alport syndrome), and their experimental mouse models. Stress is placed on the assembly of a compositionally correct GBM for the acquisition and maintenance of glomerular barrier properties.
本文总结了肾小球发生和肾小球基底膜（GBM）组装过程中的基本细胞和细胞外事件，特别关注层粘连蛋白（LM）和 IV 型胶原。还讨论了细胞表面 GBM 蛋白的受体，包括整合素、dystroglycan 和 discoidin 结构域受体 1。本文回顾了证据表明，存在于最早 GBM 中的层粘连蛋白同工型 LM-111 和成熟 GBM 中发现的最终同工型 LM-521，均来自内皮细胞和足细胞。尽管早期的胶原α1α2α1(IV) 同样来自内皮细胞和足细胞，但在完全成熟的 GBM 中发现的胶原α3α4α5(IV) 是足细胞的产物。本文还介绍了影响层粘连蛋白和 IV 型胶原合成的遗传疾病，重点介绍了 LAMB2（Pierson 综合征）和 COL4A3、COL4A4 和 COL4A5（Alport 综合征）的突变及其实验小鼠模型。强调了组装组成正确的 GBM 对于获得和维持肾小球屏障特性的重要性。
