Upregulation of TNF-α and IL-6 induces preterm premature rupture of membranes by activation of ADAMTS-9 in embryonic membrane cells
Upregulation of TNF-α and IL-6 induces preterm premature rupture of membranes by activation of ADAMTS-9 in embryonic membrane cells
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TNF-α 和 IL-6 的上调通过激活胚胎膜细胞中的 ADAMTS-9 诱导胎膜早破
DOI：
10.1016/j.lfs.2020.118237
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发表时间：
2020-11-01
期刊：
影响因子：
6.1
通讯作者：
Zhang, Rongxin
中科院分区：
文献类型：
--
作者：
Li, Wen;Zhao, Xiaomin;Zhang, Rongxin
目的：为探讨血小板反应蛋白基序9（thrombospondin motifs 9，ADAMTS 9）在早产胎膜早破（preterm premature rupture of membranes，pPROM）中的作用，材料和方法：检测24例早产、足月、有胎膜早破和无胎膜早破患者羊膜细胞中ADAMTS 9的表达。ADAMTS 9在人成釉细胞中被抑制，以研究其对胚胎膜细胞和炎症诱导的细胞损伤的影响。妊娠小鼠模型被用来评估炎症是否通过上调TNF-α和IL-6来调节ADAMTS 9，从而导致早产的发生。关键发现：我们发现ADAMTS 9蛋白和基因的表达水平在各组之间存在显著差异（pPROM >足月PROM >早产非PROM>足月非PROM）。ADAMTS 9抑制人羊膜上皮WISH细胞后，TNF-α和IL-6诱导的细胞凋亡减少。此外，与对照组相比，用LPS处理的小鼠胚胎中TNF-α、IL-6和ADAMTS 9蛋白和基因表达水平增加。在协议中，早产率较高的LPS组相比，controls.Significance：两者合计，这些在体外和体内的研究结果表明，TNF-α和IL-6分泌的巨噬细胞在炎症调节ADAMTS 9和诱导pPROM。
Aim: To investigate the role of thrombospondin motifs 9 (ADAMTS9) in preterm premature rupture of membranes (pPROM).Materials and methods: ADAMTS9 levels were measured in amnion cells from 24 patients of different groups (preterm vs. full-term birth, with vs. without PROM). ADAMTS9 was suppressed in human amnioblasts to investigate its effects on embryonic membrane cells and inflammation-induced cell damage. Pregnant mouse models were used to assess whether inflammation regulates ADAMTS9 by upregulating TNF-alpha and IL-6, contributing to the preterm birth occurrence.Key findings: We found that ADAMTS9 protein and gene expression levels significantly differed among various groups (pPROM > full-term PROM > preterm non-PROM > full-term non-PROM). After ADAMTS9 suppression in human amnioblast WISH cells, TNF-alpha- and IL-6-induced apoptosis was decreased. In addition, TNF-alpha, IL-6, and ADAMTS9 protein and gene expression levels were increased in the embryos of mice treated with LPS compared with controls. In agreement, the rate of preterm birth was higher in the LPS group compared with controls.Significance: Taken together, these in vitro and in vivo findings suggest that TNF-alpha and IL-6 secreted by macrophages during inflammation regulate ADAMTS9 and induce pPROM.