Cargando…
YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis
Pyroptosis is inflammation-associated caspase-1-dependent programmed cell death, which confers a crucial role in sepsis. The present study intends to investigate the regulatory network and function of the microarray-predicted YTHDF1 in caspase-1-dependent pyroptosis of sepsis. Peripheral blood of pa...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068740/ https://www.ncbi.nlm.nih.gov/pubmed/35508474 http://dx.doi.org/10.1038/s41420-022-00872-2 |
_version_ | 1784700283440332800 |
---|---|
author | Zhang, Shuyao Guan, Xinmin Liu, Wei Zhu, Zhe Jin, Hong Zhu, Youfeng Chen, Yun Zhang, Min Xu, Chengcheng Tang, Xu Wang, Jing Cheng, Wang Lin, Weihua Ma, Xiaoke Chen, Jianliang |
author_facet | Zhang, Shuyao Guan, Xinmin Liu, Wei Zhu, Zhe Jin, Hong Zhu, Youfeng Chen, Yun Zhang, Min Xu, Chengcheng Tang, Xu Wang, Jing Cheng, Wang Lin, Weihua Ma, Xiaoke Chen, Jianliang |
author_sort | Zhang, Shuyao |
collection | PubMed |
description | Pyroptosis is inflammation-associated caspase-1-dependent programmed cell death, which confers a crucial role in sepsis. The present study intends to investigate the regulatory network and function of the microarray-predicted YTHDF1 in caspase-1-dependent pyroptosis of sepsis. Peripheral blood of patients with sepsis was collected to determine WWP1 and YTHDF1 expression. An in vitro sepsis cell model was induced in RAW264.7 cells using lipopolysaccharide (LPS) and ATP and an in vivo septic mouse model by cecal ligation and perforation (CLP). After gain- and loss-of-function assays in vitro and in vivo, TNF-α and IL-1β levels and the cleavage of gasdermin-D (GSDMD) were detected by ELISA and Western blot assay, followed by determination of lactate dehydrogenase (LDH) activity. Immunoprecipitation and meRIP assay were performed to detect the ubiquitination of NLRP3 and the m6A modification of WWP1 mRNA. The binding of WWP1 to YTHDF1 was explored using RIP-RT-qPCR and dual luciferase gene reporter assay. It was noted that WWP1 and YTHDF1 were downregulated in clinical sepsis samples, LPS + ATP-treated RAW264.7 cells, and CLP-induced mice. The ubiquitination of NLRP3 was promoted after overexpression of WWP1. WWP1 translation could be promoted by YTHDF1. Then, WWP1 or YTHDF1 overexpression diminished LDH activity, NLRP3 inflammasomes and caspase-1-mediated cleavage of GSDMD in LPS + ATP-induced RAW264.7 cells. Overexpressed YTHDF1 restrained inflammatory response in CLP-induced mice. Collectively, the alleviatory effect of m6A reader protein YTHDF1 may be achieved through promotion of NLRP3 ubiquitination and inhibition of caspase-1-dependent pyroptosis by upregulating WWP1. |
format | Online Article Text |
id | pubmed-9068740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90687402022-05-05 YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis Zhang, Shuyao Guan, Xinmin Liu, Wei Zhu, Zhe Jin, Hong Zhu, Youfeng Chen, Yun Zhang, Min Xu, Chengcheng Tang, Xu Wang, Jing Cheng, Wang Lin, Weihua Ma, Xiaoke Chen, Jianliang Cell Death Discov Article Pyroptosis is inflammation-associated caspase-1-dependent programmed cell death, which confers a crucial role in sepsis. The present study intends to investigate the regulatory network and function of the microarray-predicted YTHDF1 in caspase-1-dependent pyroptosis of sepsis. Peripheral blood of patients with sepsis was collected to determine WWP1 and YTHDF1 expression. An in vitro sepsis cell model was induced in RAW264.7 cells using lipopolysaccharide (LPS) and ATP and an in vivo septic mouse model by cecal ligation and perforation (CLP). After gain- and loss-of-function assays in vitro and in vivo, TNF-α and IL-1β levels and the cleavage of gasdermin-D (GSDMD) were detected by ELISA and Western blot assay, followed by determination of lactate dehydrogenase (LDH) activity. Immunoprecipitation and meRIP assay were performed to detect the ubiquitination of NLRP3 and the m6A modification of WWP1 mRNA. The binding of WWP1 to YTHDF1 was explored using RIP-RT-qPCR and dual luciferase gene reporter assay. It was noted that WWP1 and YTHDF1 were downregulated in clinical sepsis samples, LPS + ATP-treated RAW264.7 cells, and CLP-induced mice. The ubiquitination of NLRP3 was promoted after overexpression of WWP1. WWP1 translation could be promoted by YTHDF1. Then, WWP1 or YTHDF1 overexpression diminished LDH activity, NLRP3 inflammasomes and caspase-1-mediated cleavage of GSDMD in LPS + ATP-induced RAW264.7 cells. Overexpressed YTHDF1 restrained inflammatory response in CLP-induced mice. Collectively, the alleviatory effect of m6A reader protein YTHDF1 may be achieved through promotion of NLRP3 ubiquitination and inhibition of caspase-1-dependent pyroptosis by upregulating WWP1. Nature Publishing Group UK 2022-05-04 /pmc/articles/PMC9068740/ /pubmed/35508474 http://dx.doi.org/10.1038/s41420-022-00872-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Shuyao Guan, Xinmin Liu, Wei Zhu, Zhe Jin, Hong Zhu, Youfeng Chen, Yun Zhang, Min Xu, Chengcheng Tang, Xu Wang, Jing Cheng, Wang Lin, Weihua Ma, Xiaoke Chen, Jianliang YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis |
title | YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis |
title_full | YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis |
title_fullStr | YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis |
title_full_unstemmed | YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis |
title_short | YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis |
title_sort | ythdf1 alleviates sepsis by upregulating wwp1 to induce nlrp3 ubiquitination and inhibit caspase-1-dependent pyroptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068740/ https://www.ncbi.nlm.nih.gov/pubmed/35508474 http://dx.doi.org/10.1038/s41420-022-00872-2 |
work_keys_str_mv | AT zhangshuyao ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT guanxinmin ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT liuwei ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT zhuzhe ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT jinhong ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT zhuyoufeng ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT chenyun ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT zhangmin ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT xuchengcheng ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT tangxu ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT wangjing ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT chengwang ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT linweihua ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT maxiaoke ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis AT chenjianliang ythdf1alleviatessepsisbyupregulatingwwp1toinducenlrp3ubiquitinationandinhibitcaspase1dependentpyroptosis |