Podocyte-specific knockout of the natriuretic peptide clearance receptor significantly reduced albuminuria and expression of fibrotic markers in a mouse model of early-stage diabetic kidney disease.
Does podocyte-specific knockout of NPRC reduce albuminuria and fibrotic markers in a mouse model of type 1 diabetes?
Inhibiting natriuretic peptide clearance by podocyte-specific knockout of NPRC attenuates albuminuria and fibrotic marker expression in a mouse model of early-stage diabetic kidney disease.
Glomerular podocytes play a key role in the pathogenesis of diabetic kidney disease (DKD). Recent studies suggest that natriuretic peptides (NPs) are podocyte protective. The beneficial effects of NPs are inhibited by the removal of NPs from the circulation by the NP clearance receptor (NPRC). To determine if inhibiting NP clearance by NPRC ameliorated DKD, we deleted NPRC specifically in glomerular podocytes in a mouse model of type 1 diabetes (Akita mice). We found that diabetes induced a significant increase in albuminuria in WT Akita mice, which was significantly reduced by knockout (KO) of NPRC. Histologic damage was mild in both WT and KO Akita mice and limited to a modest increase in mesangial matrix in both groups. In contrast, expression of the fibrotic markers fibronectin and collagen 1 was significantly increased in isolated glomerular preparations, and expression of both fibrotic markers was significantly improved by podocyte-specific KO of NPRC. Taken together, these data suggest that inhibiting NP clearance by glomerular podocytes has beneficial effects in a mouse model of early-stage DKD.
Wang et al. (Fri,) conducted a other in Diabetic kidney disease. Podocyte-specific knockout of NPRC vs. WT Akita mice was evaluated on Albuminuria and expression of fibrotic markers. Podocyte-specific knockout of the natriuretic peptide clearance receptor significantly reduced albuminuria and expression of fibrotic markers in a mouse model of early-stage diabetic kidney disease.