GNA12通过下调C5aR1-PLCβ2-PI3K-AKT-ERK1/2信号通路来调节C5a诱导的迁移。

Yu Haonan, Liu Zhihua

Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

Biophys Rep. 2023 Feb 28;9(1):33-44. doi: 10.52601/bpr.2023.230001.

has been identified as one of the reported inflammatory bowel disease (IBD) susceptibility genes in genome-wide association studies (GWAS). However, the function of GNA12 in intestinal homeostasis remains unknown. Here we report that GNA12, a G-protein α subunit, regulates C5a-induced migration in macrophages. Deficiency of GNA12 results in enhanced migration induced by C5a in macrophages. Mechanistically, GNA12 suppresses C5a-induced migration by downregulating the C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling. Therefore, our study reveals that GNA12 is an anti-inflammatory factor, which might alleviate the development of inflammation by inhibiting the excessive chemotactic migration of macrophages.

在全基因组关联研究（GWAS）中，已将其鉴定为所报道的炎症性肠病（IBD）易感基因之一。然而，GNA12在肠道内稳态中的功能仍不清楚。在此，我们报道GNA12，一种G蛋白α亚基，可调节巨噬细胞中C5a诱导的迁移。GNA12的缺乏导致巨噬细胞中C5a诱导的迁移增强。机制上，GNA12通过下调C5aR1-PLCβ2-PI3K-AKT-ERK1/2信号传导来抑制C5a诱导的迁移。因此，我们的研究表明GNA12是一种抗炎因子，它可能通过抑制巨噬细胞过度的趋化性迁移来减轻炎症的发展。