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Interleukin 1 beta‐induced calcium signaling via TRPA1 channels promotes mitogen‐activated protein kinase‐dependent mesangial cell proliferation
Author(s) -
Soni Hitesh,
Kumar Ravi,
Kanthakumar Praghalathan,
Adebiyi Adebowale
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100367r
Subject(s) - microbiology and biotechnology , mapk/erk pathway , protein kinase a , cell growth , chemistry , signal transduction , kinase , biology , biochemistry
Glomerular mesangial cell (GMC)‐derived pleiotropic cytokine, interleukin‐1 (IL‐1), contributes to hypercellularity in human and experimental proliferative glomerulonephritis. IL‐1 promotes mesangial proliferation and may stimulate extracellular matrix accumulation, mechanisms of which are unclear. The present study shows that the beta isoform of IL‐1 (IL‐1β) is a potent inducer of IL‐1 type I receptor‐dependent Ca 2+ entry in mouse GMCs. We also demonstrate that the transient receptor potential ankyrin 1 (TRPA1) is an intracellular store‐independent diacylglycerol‐sensitive Ca 2+ channel in the cells. IL‐1β‐induced Ca 2+ and Ba 2+ influxes in the cells were negated by pharmacological inhibition and siRNA‐mediated knockdown of TRPA1 channels. IL‐1β did not stimulate fibronectin production in cultured mouse GMCs and glomerular explants but promoted Ca 2+ ‐dependent cell proliferation. IL‐1β also stimulated TRPA1‐dependent ERK mitogen‐activated protein kinase (MAPK) phosphorylation in the cells. Concomitantly, IL‐1β‐induced GMC proliferation was attenuated by TRPA1 and RAF1/ MEK/ERK inhibitors. These findings suggest that IL‐1β‐induced Ca 2+ entry via TRPA1 channels engenders MAPK‐dependent mesangial cell proliferation. Hence, TRPA1‐mediated Ca 2+ signaling could be of pathological significance in proliferative glomerulonephritis.