TIGAR deficiency induces caspase-1-dependent trophoblasts pyroptosis through NLRP3-ASC inflammasome

Author:

Guo Junjun,Zhou Meijuan,Zhao Man,Li Shuxian,Fang Zhenya,Li Anna,Zhang Meihua

Abstract

IntroductionGestational diabetes mellitus (GDM), a common complication of pregnancy, is risky for both mother and fetus. Previous studies about TP53-induced glycolysis and apoptosis regulator (TIGAR) focused on the occurrence and development of cancer, cardiovascular disease, and neurological disease, however, it is still unclear whether TIGAR plays a regulatory role in gestational diabetes mellitus (GDM).MethodsUtilizing HG exposure, we explored the role of TIGAR in oxidative stress limitation, excessive inflammatory toxicity defense, and pyroptosis prevention.ResultsTIGAR was up-regulated in vivo and in vitro under HG condition, and loss of TIGAR increased ROS in trophoblast cells which drove a phenotypic switch and hindered the capacity of migration, invasion, and tube formation. This switch depended on the increased activation of NLRP3-ASC-caspase-1 signaling, which caused a distinctive characteristic of pyroptosis, and these findings could finally be reverted by antioxidant treatment (NAC) and receptor block (MCC950). Collectively, trophoblast pyroptosis is an upstream event of TIGAR deficiency-induced inflammation, which is promoted by ROS accumulation through NLRP3-ASC inflammasome.ConclusionTaken together, our results uncovered that, as the upstream event of TIGAR deficiency-induced inflammation, pyroptosis is stimulated by ROS accumulation through NLRP3-ASC inflammasome.

Funder

National Natural Science Foundation of China

Publisher

Frontiers Media SA

Subject

Immunology,Immunology and Allergy

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3