Jiang Yanmin, Pin Li, Shi Weiqun, Huang Qian, Wang Lele, Liu Huishu
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, No.9, Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Mol Cell Biochem. 2021 Jul;476(7):2791-2801. doi: 10.1007/s11010-021-04125-1. Epub 2021 Mar 15.
Term labour is associated with activation of inflammation which results in myometrial contractility, cervical ripening and decidual/membrane rupture. Serum amyloid A1 (SAA1) is an acute response protein, whose role and underlying regulatory mechanisms in human labour remain unknown. In this study, we found that the mRNA and protein expression of SAA1 in human myometrium at term was increased in labouring tissues compared to non-labouring tissues. In addition, the expression of SAA1 was significantly increased in human primary myometrial cells treated with the pro-inflammatory cytokines interleukin-1 beta (IL-1β) or tumour necrosis factor-alpha (TNF-α). Knockdown of SAA1 using siRNA (siSAA1) resulted in a significant reduction in the expression and secretion of pro-inflammatory cytokines (IL8, IL6), chemokines (CXCL5, CCL2), adhesion molecules (ICAM1, ICAM5) and contraction-associated factors (COX2, PGE2). Mechanistically, the effects of SAA1 were mediated through activation of the Yes-associated protein (YAP) pathway. There was a decrease in the protein expression of phosphorylated YAP (pYAP) after treatment of siSAA1-transfected human primary myometrial cells with IL-1β or TNF-α. Moreover, enhanced expression of YAP reversed the effect of siSAA1 on pro-labour mediators. In conclusion, these experiments demonstrated that SAA1 accelerates the inflammatory response associated with parturition by activating YAP pathway, which may be a novel understanding of the molecular mechanism of labour onset.
足月分娩与炎症激活相关，炎症会导致子宫肌层收缩、宫颈成熟和蜕膜/胎膜破裂。血清淀粉样蛋白A1（SAA1）是一种急性反应蛋白，其在人类分娩中的作用及潜在调控机制尚不清楚。在本研究中，我们发现与未分娩组织相比，足月时人类子宫肌层中SAA1的mRNA和蛋白表达在分娩组织中增加。此外，用促炎细胞因子白细胞介素-1β（IL-1β）或肿瘤坏死因子-α（TNF-α）处理的人原代子宫肌层细胞中SAA1的表达显著增加。使用小干扰RNA（siRNA，siSAA1）敲低SAA1导致促炎细胞因子（IL8、IL6）、趋化因子（CXCL5、CCL2）、黏附分子（ICAM1、ICAM5）和收缩相关因子（COX2、PGE2）的表达和分泌显著降低。从机制上讲，SAA1的作用是通过Yes相关蛋白（YAP）途径的激活介导的。在用IL-1β或TNF-α处理siSAA1转染的人原代子宫肌层细胞后，磷酸化YAP（pYAP）的蛋白表达降低。此外，YAP表达增强逆转了siSAA1对促分娩介质的作用。总之，这些实验表明SAA1通过激活YAP途径加速与分娩相关的炎症反应，这可能是对分娩发动分子机制的新认识。
