The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes.

摘要: Nephrotic syndrome is a kidney disease featured by heavy proteinuria. It caused injury to the specialized epithelial cells called "podocytes" within filtration unit of kidney, glomerulus. Previous studies showed that hyperactivation RhoGTPase, Rac1, in podocytes causes podocyte and glomerulosclerosis (accumulation extracellular matrix glomerulus). However, mechanism which Rac1 activated during unknown. Trio guanine nucleotide exchange factor (GEF) known activate Rac1. By RNA-sequencing, we found mRNA abundantly expressed cultured human podocytes. was also significantly upregulated humans with minimal change focal segmental glomerulosclerosis, two representative nephrotic syndrome. Reduced expression decreased basal activity, cell size, attachment laminin, motility. Furthermore, while pro-fibrotic cytokine, transforming growth β1 increased activity control cells, it decreases reduced expression. This likely due simultaneous activation Rac1-GTPase protein, CdGAP. Thus, important functions may contribute glomerular pathology, such as sclerosis, via activation.