安非雷古林
基因敲除
血管生成
新生血管
后肢
癌症研究
缺血
细胞生物学
免疫学
细胞凋亡
医学
生物
受体
内分泌学
内科学
表皮生长因子受体
生物化学
作者
Jin Liu,Lihong Pan,Wenxuan Hong,Siqin Chen,Peiyuan Bai,Wenyi Luo,Xiaolei Sun,Fei He,Xinlin Jia,Jia-Liang Cai,Yingjie Chen,Kai Hu,Zhenju Song,Junbo Ge,Aijun Sun
标识
DOI:10.1038/s41467-022-35159-8
摘要
Abstract Regulatory T cells (Tregs) are critically involved in neovascularization, an important compensatory mechanism in peripheral artery disease. The contribution of G protein coupled receptor 174 (GPR174), which is a regulator of Treg function and development, in neovascularization remains elusive. Here, we show that genetic deletion of GPR174 in Tregs potentiated blood flow recovery in mice after hindlimb ischemia. GPR174 deficiency upregulates amphiregulin (AREG) expression in Tregs, thereby enhancing endothelial cell functions and reducing pro-inflammatory macrophage polarization and endothelial cell apoptosis. Mechanically, GPR174 regulates AREG expression by inhibiting the nuclear accumulation of early growth response protein 1 (EGR1) via Gαs/cAMP/PKA signal pathway activation. Collectively, these findings demonstrate that GPR174 negatively regulates angiogenesis and vascular remodeling in response to ischemic injury and that GPR174 may be a potential molecular target for therapeutic interventions of ischemic vascular diseases.
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