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.
Upregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes
Disclosures: The authors declare no competing interests exist.
- Views Icon Views
- Share Icon Share
- Search Site
Shuai Hu, Runhong Han, Long Chen, Weisong Qin, Xiaodong Xu, Jingsong Shi, Xiaodong Zhu, Mingchao Zhang, Caihong Zeng, Zheng Tang, Hao Bao, Zhihong Liu; Upregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes. J Exp Med 1 February 2021; 218 (2): e20192373. doi: https://doi.org/10.1084/jem.20192373
Download citation file: