Cargando…

Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation

Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Damin, Zou, Huijuan, Liu, Jinxian, Wang, Jing, Ma, Cong, Yin, Jiaqian, Peng, Xiaoqing, Li, Danyang, Yang, Yulu, Ren, Yu, Zhang, Zhiguo, Zhou, Ping, Wang, Xiangyan, Cao, Yunxia, Xu, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732860/
https://www.ncbi.nlm.nih.gov/pubmed/35003098
http://dx.doi.org/10.3389/fimmu.2021.782792
_version_ 1784627690657021952
author Zhu, Damin
Zou, Huijuan
Liu, Jinxian
Wang, Jing
Ma, Cong
Yin, Jiaqian
Peng, Xiaoqing
Li, Danyang
Yang, Yulu
Ren, Yu
Zhang, Zhiguo
Zhou, Ping
Wang, Xiangyan
Cao, Yunxia
Xu, Xiaofeng
author_facet Zhu, Damin
Zou, Huijuan
Liu, Jinxian
Wang, Jing
Ma, Cong
Yin, Jiaqian
Peng, Xiaoqing
Li, Danyang
Yang, Yulu
Ren, Yu
Zhang, Zhiguo
Zhou, Ping
Wang, Xiangyan
Cao, Yunxia
Xu, Xiaofeng
author_sort Zhu, Damin
collection PubMed
description Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the maternal-fetal interface of unexplained recurrent spontaneous abortion (URSA) patients. The purpose of this study was to further detect the expression of HMGB1 and pyroptosis in decidual tissue of URSA patients, and explore the potential mechanism of the protective role of HMGB1 in URSA patients and mouse model. The decidua tissues of 75 URSA patients and 75 women who actively terminated pregnancy were collected, and URSA mouse models were established and treated with HMGB1 inhibitor-aspirin. The expression of HMGB1, and their receptors (RAGE, TLR2, TLR4), pyroptosis-associated proteins (NLRP-3, caspase-1, GSDMD) and NF-κB was examined at the maternal-fetal interface of human and mouse. Our study found that HMGB1, NLRP-3, Caspase-1, GSDMD, RAGE, TLR2 and TLR4 were highly expressed and NF-κB signaling pathway were activated in the decidua tissue of URSA group. Moreover, immune cell disorder and co-localization of HMGB1 and macrophages were found at the maternal-fetal interface of URSA mice. However, HMGB1, TLR2, TLR4, NF-κB, and pyroptosis-associated proteins can be down-regulated by administering low-dose aspirin. These data may indicate that highly expressed HMGB1 was actively secreted by macrophages and then activated pyroptosis through the TLR2/TLR4-NF-κB pathway to cause aseptic inflammation, leading to the occurrence and development of URSA. Moreover, low-dose aspirin can reduce HMGB1 protein levels of serum and decidual in URSA.
format Online
Article
Text
id pubmed-8732860
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-87328602022-01-07 Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation Zhu, Damin Zou, Huijuan Liu, Jinxian Wang, Jing Ma, Cong Yin, Jiaqian Peng, Xiaoqing Li, Danyang Yang, Yulu Ren, Yu Zhang, Zhiguo Zhou, Ping Wang, Xiangyan Cao, Yunxia Xu, Xiaofeng Front Immunol Immunology Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the maternal-fetal interface of unexplained recurrent spontaneous abortion (URSA) patients. The purpose of this study was to further detect the expression of HMGB1 and pyroptosis in decidual tissue of URSA patients, and explore the potential mechanism of the protective role of HMGB1 in URSA patients and mouse model. The decidua tissues of 75 URSA patients and 75 women who actively terminated pregnancy were collected, and URSA mouse models were established and treated with HMGB1 inhibitor-aspirin. The expression of HMGB1, and their receptors (RAGE, TLR2, TLR4), pyroptosis-associated proteins (NLRP-3, caspase-1, GSDMD) and NF-κB was examined at the maternal-fetal interface of human and mouse. Our study found that HMGB1, NLRP-3, Caspase-1, GSDMD, RAGE, TLR2 and TLR4 were highly expressed and NF-κB signaling pathway were activated in the decidua tissue of URSA group. Moreover, immune cell disorder and co-localization of HMGB1 and macrophages were found at the maternal-fetal interface of URSA mice. However, HMGB1, TLR2, TLR4, NF-κB, and pyroptosis-associated proteins can be down-regulated by administering low-dose aspirin. These data may indicate that highly expressed HMGB1 was actively secreted by macrophages and then activated pyroptosis through the TLR2/TLR4-NF-κB pathway to cause aseptic inflammation, leading to the occurrence and development of URSA. Moreover, low-dose aspirin can reduce HMGB1 protein levels of serum and decidual in URSA. Frontiers Media S.A. 2021-12-23 /pmc/articles/PMC8732860/ /pubmed/35003098 http://dx.doi.org/10.3389/fimmu.2021.782792 Text en Copyright © 2021 Zhu, Zou, Liu, Wang, Ma, Yin, Peng, Li, Yang, Ren, Zhang, Zhou, Wang, Cao and Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhu, Damin
Zou, Huijuan
Liu, Jinxian
Wang, Jing
Ma, Cong
Yin, Jiaqian
Peng, Xiaoqing
Li, Danyang
Yang, Yulu
Ren, Yu
Zhang, Zhiguo
Zhou, Ping
Wang, Xiangyan
Cao, Yunxia
Xu, Xiaofeng
Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation
title Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation
title_full Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation
title_fullStr Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation
title_full_unstemmed Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation
title_short Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation
title_sort inhibition of hmgb1 ameliorates the maternal-fetal interface destruction in unexplained recurrent spontaneous abortion by suppressing pyroptosis activation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732860/
https://www.ncbi.nlm.nih.gov/pubmed/35003098
http://dx.doi.org/10.3389/fimmu.2021.782792
work_keys_str_mv AT zhudamin inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT zouhuijuan inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT liujinxian inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT wangjing inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT macong inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT yinjiaqian inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT pengxiaoqing inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT lidanyang inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT yangyulu inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT renyu inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT zhangzhiguo inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT zhouping inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT wangxiangyan inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT caoyunxia inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation
AT xuxiaofeng inhibitionofhmgb1amelioratesthematernalfetalinterfacedestructioninunexplainedrecurrentspontaneousabortionbysuppressingpyroptosisactivation