MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription
Abstract 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 diabe...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-023-00637-2 |
| _version_ | 1797850006512730112 |
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| author | Nan Zhao Wei Hua Qi Liu Yueying Wang Zhiyi Liu Sinan Jin Benshuai Wang Yuxin Pang Jiping Qi Yuejia Song |
| author_facet | Nan Zhao Wei Hua Qi Liu Yueying Wang Zhiyi Liu Sinan Jin Benshuai Wang Yuxin Pang Jiping Qi Yuejia Song |
| author_sort | Nan Zhao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T18:54:27Z |
| format | Article |
| id | doaj.art-f81a0b22a31c4b6a8de5bddac7a276ed |
| institution | Directory Open Access Journal |
| issn | 1528-3658 |
| language | English |
| last_indexed | 2024-04-09T18:54:27Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-f81a0b22a31c4b6a8de5bddac7a276ed2023-04-09T11:19:23ZengBMCMolecular Medicine1528-36582023-04-0129111510.1186/s10020-023-00637-2MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcriptionNan Zhao0Wei Hua1Qi Liu2Yueying Wang3Zhiyi Liu4Sinan Jin5Benshuai Wang6Yuxin Pang7Jiping Qi8Yuejia Song9Department of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Pathology, First Clinical Hospital, Harbin Medical UniversityDepartment of Endocrinology, First Clinical Hospital, Harbin Medical UniversityAbstract 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.https://doi.org/10.1186/s10020-023-00637-2Diabetic cerebral ischemiaMALAT1PyroptosisSTAT1Cerebral ischemic reperfusion |
| spellingShingle | Nan Zhao Wei Hua Qi Liu Yueying Wang Zhiyi Liu Sinan Jin Benshuai Wang Yuxin Pang Jiping Qi Yuejia Song MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription Molecular Medicine Diabetic cerebral ischemia MALAT1 Pyroptosis STAT1 Cerebral ischemic reperfusion |
| 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 | Diabetic cerebral ischemia MALAT1 Pyroptosis STAT1 Cerebral ischemic reperfusion |
| url | https://doi.org/10.1186/s10020-023-00637-2 |
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