中南大学李吉小组宣布他们提出代谢门控血管收缩性开关：OXGR1激活机制使酒渣鼻红斑的激动剂治疗成为可能。该研究于2026年3月5日发表于国际一流学术期刊《细胞》杂志上。
课题组研究人员确定氧戊二酸（α-KG）是患者中与酒渣鼻相关的代谢物升高并与红斑严重程度相关。外源性α-KG给药可改善小鼠模型中酒渣鼻样表现。机制上，α-KG激活血管平滑层细胞（VSMC）富集的G蛋白偶联受体（GPCR） OXGR1，诱导Gq信号传导，增强MYL9磷酸化，促进VSMC收缩，限制血管舒张。与α-KG或衣康酸结合的OXGR1-Gq复合物的低温电镜（cryo-EM）结构揭示了识别其内源性受体激动剂的特异性双酸袋及其不同于经典GPCR的激活机制。基于这些结构，小组开发了A-1，一种合成选择性OXGR1激动剂，可减轻红斑和炎症，其疗效与一线治疗相当，同时在酒渣鼻样模型中提供更高的安全性。这些发现将代谢物与血管功能障碍联系起来，并提名OXGR1激动剂用于红斑和血管疾病的精确治疗。
据介绍，酒渣鼻是一种炎症性皮肤病，由于病理性血管舒张介导的红斑的治疗效果有限，使其陷入困境。
附：英文原文
Title: Metabolite-gated vascular contractility switch: OXGR1 activation mechanism enables agonist therapy for rosacea erythema
Author: Wenqin Xiao, Yan Zhu, Xinjie Tang, Kongkai Zhu, Weifeng Zhang, Mengting Chen, Kui Cai, San Xu, Zheng Wu, Mei Wang, Jiayi Liu, Linglong Long, Zixin Tan, Aike Wu, Songqi Zhou, Zhixiang Zhao, Yan Tang, Yingxue Huang, Ben Wang, Fangfen Liu, Qian Wang, Fan Yang, Dan Jian, Wei Shi, Hongfu Xie, Xiang Chen, Lulu Guo, Zhili Deng, Jinpeng Sun, Ji Li
Issue&Volume: 2026-03-05
Abstract: Rosacea, an inflammatory skin disorder, poses a dilemma owing to limited effectiveness of treatments for pathological vasodilation-mediated erythema. Here, we identify oxoglutaric acid (α-KG) as a rosacea-associated metabolite elevated in patients and correlated with erythema severity. Exogenous α-KG administration ameliorates rosacea-like manifestations in murine models. Mechanistically, α-KG activates OXGR1, a vascular smooth muscle cell (VSMC)-enriched G protein-coupled receptor (GPCR) to induce Gq signaling and enhance MYL9 phosphorylation, promoting VSMC contraction and limiting vasodilation. Cryo-electron microscopy (cryo-EM) structures of OXGR1-Gq complexes bound to α-KG or itaconate reveal a specific bipartite-acid pocket recognizing its endogenous agonist and an activation mechanism distinct from classical GPCRs. Building on these structures, we developed A-1, a synthetic selective OXGR1 agonist that mitigates erythema and inflammation with efficacy comparable to first-line therapy while offering enhanced safety in rosacea-like models. These findings link a metabolite to vascular dysfunction and nominate OXGR1 agonism for precision treatment of erythema and vascular disorders.
DOI: 10.1016/j.cell.2026.01.036
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00164-9