TAK1 may promote the development of diabetic nephropathy by reducing the stability of SnoN protein.

AIMS:This study aimed to investigate the role of transforming growth factor-β-activated protein kinase 1(TAK1) in the development of diabetic nephropathy (DN) by regulating the protein stability of Ski-related novel protein N(SnoN). MAIN METHODS:A combination of in vivo and in vitro model systems was used to investigate how TAK1 regulated the expression of SnoN protein in DN. The study determined the effects of modulating the expression or activity of TAK1 on the SnoN protein level and its influence on the epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. KEY FINDINGS:Under the high-glucose condition, the activation of TGF-β1/TAK1-induced phosphorylation and ubiquitination of SnoN protein resulted in reduced SnoN protein level as a consequence of enhanced SnoN degradation, which promoted EMT and ECM deposition in renal tubular epithelial cells. The study showed that TAK1 impaired SnoN protein level by decreasing the protein stability of SnoN. SIGNIFICANCE:TAK1 mediated the phosphorylation of SnoN, resulting in SnoN ubiquitination and eventual degradation, which enhanced EMT and ECM deposition to promote renal fibrosis during DN.

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