The E3 ubiquitin ligase TRIM31 plays a critical role in hypertensive nephropathy by promoting proteasomal degradation of MAP3K7 in the TGF-β1 signaling pathway

Renal fibrosis and inflammation are critical for the initiation and progression of hypertensive renal disease (HRD). However, the signaling mechanisms underlying their induction are poorly understood, and the role of tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase, in HRD remains unclear. This study aimed to elucidate the role of TRIM31 in the pathogenesis of HRD, discover targets of TRIM31, and explore the underlying mechanisms. Pathological specimens of human HRD kidney were collected and an angiotensin II (AngII)-induced HRD mouse model was developed. We found that TRIM31 was markedly reduced in both human and mouse HRD renal tissues. A TRIM31 -/- mice was thus constructed and showed significantly aggravated hypertension-induced renal dysfunction, fibrosis, and inflammation, following chronic AngII infusion…