Department of Anatomy, Kyorin University School of Medicine, Tokyo, Japan.
Department of Anatomy and Life Structure, Juntendo University School of Medicine, Tokyo, Japan.
J Am Soc Nephrol. 2024 Oct 1;35(10):1366-1380. doi: 10.1681/ASN.0000000000000427. Epub 2024 Jun 6.
Deletion of endothelial receptor adhesion G-protein–coupled receptor F5 in mice led to abnormal structural and functional properties of the glomerular filtration barrier. Adhesion G-protein–coupled receptor F5 regulates gene expression of glomerular basement membrane components and a mechanosensitive transcription factor.
Glomerular endothelial cells are recognized to be important for maintaining the glomerular filtration barrier. Adhesion G-protein–coupled receptor F5 (ADGRF5), an adhesion G protein–coupled receptor, has been suggested to be involved in endothelial cell function. However, the role of ADGRF5 in the glomerular filtration barrier integrity remains elusive.
Cellular expression of ADGRF5 in mouse glomerulus was determined by histological analyses. The effect of ADGRF5 deletion on the glomerular morphology, kidney function, and glomerular endothelial gene/protein expression was then analyzed using ADGRF5 knockout () mice and human primary glomerular endothelial cells.
ADGRF5 was specifically expressed in the capillary endothelial cells within the glomerulus. mice developed albuminuria and impaired kidney function with morphological defects in the glomeruli, namely glomerular hypertrophy, glomerular basement membrane splitting and thickening, diaphragmed fenestration and detachment of the glomerular endothelial cells, and mesangial interposition. These defects were accompanied by the altered expression of genes responsible for glomerular basement membrane organization (type 4 collagens and laminins) and Krüppel-like factor 2 () in glomerular endothelial cells. Moreover, knockdown decreased and expression and increased expression in human primary glomerular endothelial cells.
The loss of ADGRF5 resulted in altered gene expression in glomerular endothelial cells and perturbed the structure and permselectivity of the glomerular filtration barrier.
删除小鼠内皮细胞受体黏附 G 蛋白偶联受体 F5 导致肾小球滤过屏障的结构和功能异常。黏附 G 蛋白偶联受体 F5（ADGRF5）调节肾小球基底膜成分和机械敏感转录因子的基因表达。
肾小球内皮细胞被认为对维持肾小球滤过屏障很重要。黏附 G 蛋白偶联受体 F5（ADGRF5）作为一种黏附 G 蛋白偶联受体，被认为参与内皮细胞功能。然而，ADGRF5 在肾小球滤过屏障完整性中的作用仍不清楚。
通过组织学分析确定 ADGRF5 在小鼠肾小球中的细胞表达。然后使用 ADGRF5 敲除（）小鼠和人原代肾小球内皮细胞分析 ADGRF5 缺失对肾小球形态、肾功能和肾小球内皮基因/蛋白表达的影响。
ADGRF5 特异性表达在肾小球中的毛细血管内皮细胞中。 小鼠出现白蛋白尿和肾功能受损，肾小球形态学缺陷，包括肾小球肥大、肾小球基底膜分裂和增厚、膈状窗孔和肾小球内皮细胞分离以及系膜插入。这些缺陷伴随着负责肾小球基底膜组织的基因（IV 型胶原和层粘连蛋白）和 Krüppel 样因子 2（）的表达改变在肾小球内皮细胞中。此外， 在人原代肾小球内皮细胞中敲低降低了 和 的表达，增加了 的表达。
ADGRF5 的缺失导致肾小球内皮细胞基因表达改变，并扰乱了肾小球滤过屏障的结构和选择性。
