Affiliation:
1. National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
2. National Standard Laboratory of Pharmacology for Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
Abstract
Podocyte injury is a common hallmark in various glomerular diseases. The level of LRRC55 was increased in podocytes of patients with focal segmental glomerulosclerosis (FSGS), diabetic nephropathy (DN), and membranous nephropathy (MN). Upregulated LRRC55 and increased intracellular Ca2+ led to BK channel activation and the loss of intracellular potassium, resulting in apoptosome formation and caspase-3 activation in angiotensin II (Ang II)–treated podocytes. Knockout of Lrrc55 or the BK channel prevented the BK current and ameliorated podocyte injury in Ang II–treated mice. Upstream, NFATc3 regulated the expression of LRRC55. Increased LRRC55 expression in podocytes was also evident in animal models of FSGS, DN, and MN. Treatment with losartan or LRRC55 siRNA suppressed LRRC55 expression, prevented BK channel activation, and attenuated podocyte injury in animal models of FSGS, DN, and MN. In conclusion, upregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes in FSGS, DN, and MN. LRRC55 inhibition may represent a new therapeutic approach for podocyte injury.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Deng Feng Scholars of Nanjing University
Fundamental Research Funds for the Central Universities
National Key Research and Development Program of China
Major International (Regional) Joint Research Programme
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
14 articles.
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