Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Matrix Biol. 2018 Oct;71-72:250-261. doi: 10.1016/j.matbio.2018.04.008. Epub 2018 Apr 16.
The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy. Mutations in LAMB2 that impact the synthesis or function of laminin α5β2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome. The very different types of kidney diseases that result from mutations in collagen IV vs. laminin are likely due to very different pathogenic mechanisms. A better understanding of these mechanisms should lead to targeted therapeutic approaches that can help people with these rare but important diseases.
肾小球基底膜 (GBM) 是肾脏肾小球滤过屏障的重要组成部分。与所有基底膜一样，GBM 包含 IV 型胶原、层粘连蛋白、巢蛋白和硫酸乙酰肝素蛋白聚糖。它被足细胞和肾小球内皮细胞包围，这些细胞既能合成 GBM，又能黏附于 GBM。影响 GBM 胶原 α3α4α5(IV) 成分的突变会导致 Alport 综合征（伴有不同程度的耳眼缺陷的肾脏疾病）及其变体，包括薄基底膜肾病。影响层粘连蛋白 α5β2γ1 (LM-521) 合成或功能的 LAMB2 突变会导致 Pierson 综合征（伴有眼和神经缺陷的先天性肾病综合征）及其较轻的变体，包括孤立性先天性肾病综合征。由于 IV 型胶原与层粘连蛋白突变导致的肾脏疾病类型非常不同，可能是由于非常不同的发病机制所致。更好地了解这些机制应能导致靶向治疗方法，帮助这些罕见但重要疾病的患者。
