Glomerular transcriptome changes associated with lipopolysaccharide-induced proteinuria

American Journal of Nephrology
Ying SunChrister Betsholtz

Abstract

Global gene expression patterns have recently been characterized in normal glomeruli, but gene expression changes that accompany glomerular disease remain poorly characterized. Here, we mapped global glomerular gene expression profile changes occurring in conjunction with lipopolysaccharide (LPS)-induced proteinuria in mice. We observed dramatic transcriptional reprogramming in glomeruli in response to LPS, representing some 20% of all genes and about 45% of the genes that are normally highly expressed in glomeruli. Bioinformatic analysis revealed significant changes in transcripts encoding proteins involved in the regulation of adherence junctions, actin cytoskeleton and survival in podocytes. In the LPS-treated mice, we observed dysregulation of genes expressed in glomerular endothelial and mesangial cells and in podocytes, there was also a significant decrease in podocyte number. Moreover, collagen alpha1, alpha2 (IV) and laminin 10 (laminin alpha 5 beta 1 gamma 1), which are expressed in immature glomeruli, were upregulated in the glomeruli of LPS-treated mice, suggesting remodeling of the glomerular basement membrane and activation of mesangial cells. By superimposing the LPS-induced changes onto GlomNet, a protein-protein...Continue Reading

Citations

Apr 12, 2012·The Journal of Biological Chemistry·Sandeep K MallipattuJohn C He
May 21, 2010·Science Signaling·Shao-Yu ZhangDjillali Sahali
Sep 29, 2011·Journal of the American Society of Nephrology : JASN·Yukino NishiboriKarl Tryggvason
May 14, 2011·Journal of the American Society of Nephrology : JASN·Bing HeChrister Betsholtz
Nov 20, 2012·Journal of Cell Communication and Signaling·Tarak SrivastavaChristopher J Harrison
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