Open AccessNF-κB-dependent upregulation of (pro)renin receptor mediates high-NaCl-induced apoptosis in mouse inner medullary collecting duct cells
Author(s) -
Jiahui Su,
Xiyang Liu,
Chuanming Xu,
Xiaohan Lu,
Fei Wang,
Hui Fang,
Aihua Lu,
Qixiang Qiu,
Chunling Li,
Tianxin Yang
Publication year - 2017
Publication title -
american journal of physiology. cell physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.432
H-Index - 181
eISSN - 1522-1563
pISSN - 0363-6143
DOI - 10.1152/ajpcell.00068.2017
Subject(s) - downregulation and upregulation , apoptosis , small interfering rna , gene silencing , chemistry , microbiology and biotechnology , nf κb , receptor , transfection , biology , biochemistry , gene
(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/kgH 2 O 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-κB p65 protein. NF-κB inhibition with QNZ, caffeic acid phenethyl ester, or small interfering RNA (siRNA)-mediated silencing of NF-κB 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-κB p65. These results show that induction of PRR expression by exposure to high NaCl occurs through activation of NF-κB, thus contributing to cell apoptosis.