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.
Keywords: NF-κB pathway; TGF-β/Smad; inflammatory response; mindin; renal fibrosis.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.