NF-?B-dependent upregulation of (pro)renin receptor mediates high-NaCl-induced apoptosis in mouse inner medullary collecting duct cells.

ABSTRACT: (Pro)renin receptor (PRR), a component of the renin-angiotensin system, has emerged as a new regulator of collecting duct function. The present study was designed to investigate the role of PRR in high salt-induced apoptosis in cultured mouse inner medullary collecting duct cells, mIMCD-K2 cells. Exposure to high NaCl at 550 mosM/kgH2O increased PRR protein abundance, as did exposure to mannitol, sodium gluconate, or choline chloride. This was accompanied by upregulation of the abundance of phosphorylated NF-?B p65 protein. NF-?B inhibition with QNZ, caffeic acid phenethyl ester, or small interfering RNA (siRNA)-mediated silencing of NF-?B p65 attenuated high-NaCl-induced PRR upregulation. Exposure to high salt for 24 h induced apoptosis, as assessed by immunoblotting and immunocytochemistry analysis of cleaved caspase-3 and flow cytometry analysis of the number of apoptotic cells. High-NaCl-induced apoptosis was attenuated by a PRR decoy inhibitor, PRO20, or siRNA-mediated silencing of NF-?B p65. These results show that induction of PRR expression by exposure to high NaCl occurs through activation of NF-?B, thus contributing to cell apoptosis.

SUBMITTER: Su J 

PROVIDER: S-EPMC5814589 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature