Neuromedin U aggravates medial arterial calcification via the activation of receptor NMUR1-mediated ERK signal pathway in rats with chronic kidney disease.

Authors

Rui Chang, Hong-Yu Wang, Wen-Juan Cao, Han-Xu Zhu, Rong-Jie Tang, Qing Gao, Ye-Bo Zhou, Lei-Lei Chen

Published in

Cellular signalling. Pages 112893. Sep 13, 2026. Epub Sep 13, 2026.

Abstract

Medial arterial calcification (MAC) is closely related to the morbidity and mortality in people with chronic kidney disease (CKD). Neuromedin U (NMU) is a group of highly conserved neuropeptides, and it exerts its peripheral effects mainly via NMU receptors, NMUR1. The present study was designed to explore the role and mechanism of NMU in MAC under condition of CKD. CKD rats with MAC were induced by feeding an adenine (0.75%) diet combined with high phosphorus (1.5%) for 4 weeks. Rat NMU (NMU-23, 1 nM/kg/h) infusion was applied subcutaneously via osmotic pump. The calcified vascular smooth muscle cells (VSMCs, A7r5 cell line) were induced by the calcifying media. In the aortic media of rats with CKD and in the calcifying media-treated VSMCs, the results showed that the endogenous protein levels of NMU and its receptors NMUR1 and NMUR2 were elevated, and NMU application further aggravated calcification and promoted osteogenic transformation and apoptosis. These effects were effectively inhibited by an inhibitor of ERK activation U0126 and NMUR1 antagonist CPN-351, but not NMUR2 antagonist R-PSOP, in the calcifying media-treated VSMCs. Moreover, the downregulation of NMUR1 expression using siRNA, but not NMUR2 downregulation, significantly attenuated the promoting effects of NMU on calcification, osteogenic transformation and apoptosis in cacified VSMCs. Our research suggests that the role of NMU in calcification of VSMCs partially through the activation of the receptor NMUR1-ERK signaling pathway. So downregulating the expressions of NMU and NMUR1 in aortic media may be a good strategy for the treatment of MAC in CKD.

PMID:
42732809
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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