Cargando…
MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription
BACKGROUND: Dysregulated long non-coding RNAs participate in the development of diabetic cerebral ischemia. This study aimed to investigate the underlying mechanism of lncRNA MALAT1 in diabetic cerebral ischemia. METHOD: Middle cerebral artery occlusion (MCAO) was performed to establish diabetic cer...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069069/ https://www.ncbi.nlm.nih.gov/pubmed/37013491 http://dx.doi.org/10.1186/s10020-023-00637-2 |
_version_ | 1785018787066544128 |
---|---|
author | Zhao, Nan Hua, Wei Liu, Qi Wang, Yueying Liu, Zhiyi Jin, Sinan Wang, Benshuai Pang, Yuxin Qi, Jiping Song, Yuejia |
author_facet | Zhao, Nan Hua, Wei Liu, Qi Wang, Yueying Liu, Zhiyi Jin, Sinan Wang, Benshuai Pang, Yuxin Qi, Jiping Song, Yuejia |
author_sort | Zhao, Nan |
collection | PubMed |
description | BACKGROUND: Dysregulated long non-coding RNAs participate in the development of diabetic cerebral ischemia. This study aimed to investigate the underlying mechanism of lncRNA MALAT1 in diabetic cerebral ischemia. METHOD: Middle cerebral artery occlusion (MCAO) was performed to establish diabetic cerebral I/R in vivo. TTC and neurological deficits assessment were performed to assess cerebral ischemic injury. LDH was conducted to detect cytotoxicity. RT-qPCR and western blotting assays were applied to determine mRNA and protein expression. Flow cytometry was performed to detect the pyroptosis of BV2 cells. Immunofluorescence and FISH were conducted for subcellular localization of MALAT1 and STAT1. ELISA was performed to determine cytokine release. Dual luciferase reporter, RIP, and ChIP assays were used to validate the interaction between STAT1 and MALAT1/NLRP3. Diabetes aggravated cerebral injury in vivo and in vitro. Diabetic cerebral ischemia induced inflammatory response and inflammation-induced cell pyroptosis. RESULT: MALAT1 was overexpressed in diabetic cerebral ischemia models in vivo and in vitro. However, knockdown of MALAT1 suppressed inflammatory response and the pyroptosis of BV2 cells. Moreover, MALAT1 interacted with STAT1 to transcriptionally activate NLRP3. Knockdown of STAT1 significantly reversed the effects of MALAT1. Furthermore, STAT1 promotes the MALAT1 transcription. MALAT1 interacts with STAT1 to promote the pyroptosis of microglias induced by diabetic cerebral ischemia through activating NLRP3 transcription. CONCLUSION: Thus, knockdown of MALAT1 may be a potential promising therapy target for diabetic cerebral ischemia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00637-2. |
format | Online Article Text |
id | pubmed-10069069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100690692023-04-04 MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription Zhao, Nan Hua, Wei Liu, Qi Wang, Yueying Liu, Zhiyi Jin, Sinan Wang, Benshuai Pang, Yuxin Qi, Jiping Song, Yuejia Mol Med Research Article BACKGROUND: Dysregulated long non-coding RNAs participate in the development of diabetic cerebral ischemia. This study aimed to investigate the underlying mechanism of lncRNA MALAT1 in diabetic cerebral ischemia. METHOD: Middle cerebral artery occlusion (MCAO) was performed to establish diabetic cerebral I/R in vivo. TTC and neurological deficits assessment were performed to assess cerebral ischemic injury. LDH was conducted to detect cytotoxicity. RT-qPCR and western blotting assays were applied to determine mRNA and protein expression. Flow cytometry was performed to detect the pyroptosis of BV2 cells. Immunofluorescence and FISH were conducted for subcellular localization of MALAT1 and STAT1. ELISA was performed to determine cytokine release. Dual luciferase reporter, RIP, and ChIP assays were used to validate the interaction between STAT1 and MALAT1/NLRP3. Diabetes aggravated cerebral injury in vivo and in vitro. Diabetic cerebral ischemia induced inflammatory response and inflammation-induced cell pyroptosis. RESULT: MALAT1 was overexpressed in diabetic cerebral ischemia models in vivo and in vitro. However, knockdown of MALAT1 suppressed inflammatory response and the pyroptosis of BV2 cells. Moreover, MALAT1 interacted with STAT1 to transcriptionally activate NLRP3. Knockdown of STAT1 significantly reversed the effects of MALAT1. Furthermore, STAT1 promotes the MALAT1 transcription. MALAT1 interacts with STAT1 to promote the pyroptosis of microglias induced by diabetic cerebral ischemia through activating NLRP3 transcription. CONCLUSION: Thus, knockdown of MALAT1 may be a potential promising therapy target for diabetic cerebral ischemia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-023-00637-2. BioMed Central 2023-04-03 /pmc/articles/PMC10069069/ /pubmed/37013491 http://dx.doi.org/10.1186/s10020-023-00637-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhao, Nan Hua, Wei Liu, Qi Wang, Yueying Liu, Zhiyi Jin, Sinan Wang, Benshuai Pang, Yuxin Qi, Jiping Song, Yuejia MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription |
title | MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription |
title_full | MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription |
title_fullStr | MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription |
title_full_unstemmed | MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription |
title_short | MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription |
title_sort | malat1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating stat1 mediated nlrp3 transcription |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069069/ https://www.ncbi.nlm.nih.gov/pubmed/37013491 http://dx.doi.org/10.1186/s10020-023-00637-2 |
work_keys_str_mv | AT zhaonan malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT huawei malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT liuqi malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT wangyueying malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT liuzhiyi malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT jinsinan malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT wangbenshuai malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT pangyuxin malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT qijiping malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription AT songyuejia malat1knockdownalleviatesthepyroptosisofmicrogliasindiabeticcerebralischemiaviaregulatingstat1mediatednlrp3transcription |