S100A16 promotes acute kidney injury by activating HRD1-induced ubiquitination and degradation of GSK3β and CK1α

• DOI: 10.1007/s00018-022-04213-5
• Publication Date: 2022-03-12T20:02:46Z
• Authors: Yifei Sun; Ya Fan; Zheng Wang; Min Li; Dongming Su; Yun Liu; Xiubin Liang
• Keywords: Degradation

The pathogenesis of acute kidney injury (AKI) is associated with the activation multiple signaling pathways, including Wnt/β-catenin signaling. However, mechanism pathway in renal interstitial fibroblasts during AKI unclear. S100 calcium-binding protein A16 (S100A16), a new member family, multi-functional factor involved various pathogenies, tumors, glycolipid metabolism disorder, and chronic disease (CKD). We investigated potential participation S100A16 by subjecting wild-type (WT) knockout (S100A16+/-) mice to ischemia-reperfusion (IRI), revealed upregulation this model, which impeded recovered expression downstream hepatocyte growth (HGF). also found that was highly expressed Platelet-derived receptor beta (PDGFRβ) positive vivo. Consistently, rat (NRK-49F cells), both hypoxia/reoxygenation overexpression exacerbated apoptosis inhibited HGF secretion; whereas knockdown or inhibitor ICG-001 reversed these changes. Mechanistically, we showed promoted via ubiquitylation degradation β-catenin complex members, glycogen synthase kinase 3β (GSK3β) casein 1α (CK1α), mediated E3 ubiquitin ligase, HMG-CoA reductase 1 (HRD1). Our study identified as key regulator AKI.