PROFILING MOLECULAR SIGNALS ASSOCIATED WITH PODOCYTE EFFACEMENT IN MINIMAL CHANGE NEPHROTIC SYNDROME FOLLOWING THE TH2 CYTOKINE STIMULATION

CHAN CHANG YIEN

Publication

PROFILING MOLECULAR SIGNALS ASSOCIATED WITH PODOCYTE EFFACEMENT IN MINIMAL CHANGE NEPHROTIC SYNDROME FOLLOWING THE TH2 CYTOKINE STIMULATION

CHAN CHANG YIEN

Abstract

This study aimed to delineate the glomerular ?gene signature? related to our IL-13 rat model of minimal change nephrotic syndrome through microarray analysis, and subsequently to validate this in cultured human podocytes in order to investigate the mechanism of IL-13-induced B7-1 danger signaling in causing podocyte injury. Gene expression of vav1 was highly upregulated in the glomeruli of IL-13 overexpressed rats and MetaCore pathway analysis of the DEGs suggested a possible novel role of vav1 in podocyte cytoskeleton remodeling. We confirmed the presence of vav1 both in glomeruli and podocytes by immunohistological staining. In vitro IL-13 stimulation in podocytes resulted in significant increased expression of IL-13Ra2, B7-1 and phosphorylated vav1. This was associated with actin cytoskeleton rearrangement and Rac1 activation, which was abrogated in vav1 knock-down podocytes. In conclusion, IL-13 induced podocyte FP effacement in our rat model of MCNS was mediated through activation of B7-1-vav1-Rac1 induced actin cytoskeleton rearrangement.