Albumin induces CD44 expression in glomerular parietal epithelial cells by activating the ERK signaling pathway

Abstract

De novo expression of CD44 in glomerular parietal epithelial cells (PECs) leads to a pro‐sclerotic and migratory PEC phenotype in focal segmental glomerulosclerosis. However, the mechanisms underlying CD44 induction in activated PECs remain largely unknown. This study was performed to examine CD44 expression in rat PECs under proteinuric condition and its regulatory mechanisms. CD44 gene and protein levels were examined in Zucker diabetic (ZD) rat kidneys and primary cultured rat PECs exposed to exogenous albumin. Gene microarray and real‐time PCR confirmed an upregulation of CD44 mRNA in renal cortex and glomeruli of ZD rats. Immunofluorescence staining of kidney sections revealed an increase in CD44 signal in claudin‐1‐positive PECs. Enhanced CD44 staining was observed in activated PECs localized in Bowman's capsule and migrated into the glomerular tuft. Moreover, anti‐proteinuric treatment with losartan, an angiotensin II receptor blocker, significantly reduced CD44 protein level in the diabetic rat kidney. In primary cultured rat PECs, administration of rat serum albumin (RSA, 0.25 – 1 mg/ml) resulted in an activation of ERK1/2 MAPK signaling and upregulation of CD44 and claudin‐1 protein expression. This increase in claudin‐1 and CD44 protein was significantly attenuated in the presence of specific ERK1/2 inhibitor U0126. Taken together, our results demonstrate that albumin activates PECs and induces CD44 expression, at least partially via the activation of ERK signaling pathway.Support or Funding InformationNIH SC1DK112151, NIH/NCRR/RCMI 8G12MD007602 & 8U54MD007588This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.