Open AccessMindin deficiency alleviates renal fibrosis through inhibiting NF‐κB and TGF‐β/Smad pathways
Author(s) -
Yang Kang,
Li Wei,
Bai Tao,
Xiao Yusha,
Yu Weimin,
Luo Pengcheng,
Cheng Fan
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15236
Subject(s) - kidney , fibrosis , smad , signal transduction , cancer research , transforming growth factor , biology , medicine , pathology , endocrinology , microbiology and biotechnology
Renal fibrosis acts as a clinical predictor in patients with chronic kidney disease and is characterized by excessive extracellular matrix (ECM) accumulation. Our previous study suggested that mindin can function as a mediator for liver steatosis pathogenesis. However, the role of mindin in renal fibrosis remains obscure. Here, tumour necrosis factor (TGF)‐β‐treated HK‐2 cells and global mindin knockout mouse were induced with renal ischaemia reperfusion injury (IRI) to test the relationship between mindin and renal fibrosis. In vitro, mindin overexpression promoted p65—the hub subunit of the NF‐κB signalling pathway—translocation from the cytoplasm into the nucleus, resulting in NF‐κB pathway activation in TGF‐β‐treated HK‐2 cells. Meanwhile, mindin activated the TGF‐β/Smad pathway, thereby causing fibrotic‐related protein expression in vitro. Mindin −/− mice exhibited less kidney lesions than controls, with small renal tubular expansion, inflammatory cell infiltration, as well as collagen accumulation, following renal IRI. Mechanistically, mindin −/− mice suppressed p65 translocation and deactivated NF‐κB pathway. Simultaneously, mindin disruption inhibited the TGF‐β/Smad pathway, alleviating the expression of ECM‐related proteins. Hence, mindin may be a novel target of renal IRI in the treatment of renal fibrogenesis.