Open AccessUpregulated LRRC55 promotes BK channel activation and aggravates cell injury in podocytes
Author(s) -
Tianjun Zhou,
Ruiming Han,
Long Chen,
Weisong Qin,
Xiaodong Xu,
Jingsong Shi,
Xiaodong Zhu,
Mingchao Zhang,
Caihong Zeng,
Zheng Tang,
Hanying Bao,
Zhihong Liu
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20192373
Subject(s) - podocyte , bk channel , nephrin , downregulation and upregulation , diabetic nephropathy , focal segmental glomerulosclerosis , glomerulosclerosis , endocrinology , membranous nephropathy , chemistry , medicine , microbiology and biotechnology , kidney , potassium channel , biology , glomerulonephritis , proteinuria , biochemistry , gene
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.