Urantide alleviates atherosclerosis-related liver and kidney injury via the Wnt/β-catenin signaling pathway in ApoE(-/-) mice.

Abstract

OBJECTIVE: To investigate the role of urantide in the prevention and treatment of atherosclerosis (AS)-related liver and kidney injury by antagonizing the urotensin II/urotensin receptor (UII/UT) system and regulating the Wnt/β-catenin signaling pathway. METHODS: Atherosclerotic ApoEmice were treated with 20 mg/kg, 30 mg/kg, and 40 mg/kg urantide for 14 days. RESULTS: When ApoEmice developed AS, significant pathological changes occurred in the liver and kidney, and the UII/UT system in tissue was highly activated; furthermore, the Wnt/β-catenin signalling pathway was activated, and proteins related to this signalling pathway, such as GSK-3β, AXIN2, CK‑1, and APC, were significantly downregulated. After urantide treatment, the pathological damage to the liver and kidney was effectively improved, the activity of the UII/UT system was effectively inhibited, and the expression of the Wnt/β-catenin signalling pathway and related proteins was restored. Wnt/β-catenin signals were mainly localized in the cytoplasm, renal tubules, and interstitium. CONCLUSION: Urantide could improve AS-related liver and kidney injury by antagonizing the UII/UT system, and the improvements in liver and kidney function in atherosclerotic ApoEmice may be related to inhibition of the Wnt/β-catenin signalling pathway.