MALAT1 knockdown alleviates myocardial injury in mice with severe acute pancreatitis via the miR-374a/Sp1/Wnt/β-catenin pathway
AJTR Copyright © 2023..
BACKGROUND: Severe acute pancreatitis (SAP) contributes to high mortality (as high as 30%) and multiple organ injuries. In this study, we established a mouse model with SAP to detect biomolecules implicated in myocardial injury and to expound the signal transduction pathway involved.
METHODS: A SAP mouse model was established to assess inflammation- and myocardial injury-related markers. Also, pancreatic and myocardial injuries and cardiomyocyte apoptosis were evaluated. Microarray analysis was implemented to filter differentially expressed long non-coding RNAs (lncRNAs) in myocardial tissues of normal and SAP mice. Then, miRNA-based microarray analysis and bioinformatics prediction were performed to probe the downstream molecules of MALAT1, followed by rescue experiments.
RESULTS: SAP mice showed pancreatic and myocardial injuries and increased apoptosis of cardiomyocytes. MALAT1 was expressed highly in SAP mice, and inhibition of MALAT1 reduced myocardial injury and cardiomyocyte apoptosis in SAP mice. MALAT1 was found to localize to the cytoplasm of cardiomyocytes and bind to miR-374a. Inhibition of miR-374a inhibited the alleviating effects of MALAT1 knockdown on the myocardial injury. miR-374a targeted Sp1, and Sp1 silencing reversed the promoting effects of miR-374a inhibitor on myocardial injury. Sp1 regulated myocardial injury in SAP via the Wnt/β-catenin pathway.
CONCLUSION: MALAT1 promotes myocardial injury complicated by SAP via the miR-374a/Sp1/Wnt/β-catenin pathway.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
American journal of translational research - 15(2023), 6 vom: 30., Seite 3928-3941 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Yan [VerfasserIn] |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Revised 18.07.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359356931 |
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| 100 | 1 | |a Sun, Yan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MALAT1 knockdown alleviates myocardial injury in mice with severe acute pancreatitis via the miR-374a/Sp1/Wnt/β-catenin pathway |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Revised 18.07.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a AJTR Copyright © 2023. | ||
| 520 | |a BACKGROUND: Severe acute pancreatitis (SAP) contributes to high mortality (as high as 30%) and multiple organ injuries. In this study, we established a mouse model with SAP to detect biomolecules implicated in myocardial injury and to expound the signal transduction pathway involved | ||
| 520 | |a METHODS: A SAP mouse model was established to assess inflammation- and myocardial injury-related markers. Also, pancreatic and myocardial injuries and cardiomyocyte apoptosis were evaluated. Microarray analysis was implemented to filter differentially expressed long non-coding RNAs (lncRNAs) in myocardial tissues of normal and SAP mice. Then, miRNA-based microarray analysis and bioinformatics prediction were performed to probe the downstream molecules of MALAT1, followed by rescue experiments | ||
| 520 | |a RESULTS: SAP mice showed pancreatic and myocardial injuries and increased apoptosis of cardiomyocytes. MALAT1 was expressed highly in SAP mice, and inhibition of MALAT1 reduced myocardial injury and cardiomyocyte apoptosis in SAP mice. MALAT1 was found to localize to the cytoplasm of cardiomyocytes and bind to miR-374a. Inhibition of miR-374a inhibited the alleviating effects of MALAT1 knockdown on the myocardial injury. miR-374a targeted Sp1, and Sp1 silencing reversed the promoting effects of miR-374a inhibitor on myocardial injury. Sp1 regulated myocardial injury in SAP via the Wnt/β-catenin pathway | ||
| 520 | |a CONCLUSION: MALAT1 promotes myocardial injury complicated by SAP via the miR-374a/Sp1/Wnt/β-catenin pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Long non-coding RNA MALAT1 | |
| 650 | 4 | |a Sp1 | |
| 650 | 4 | |a Wnt/β-catenin pathway | |
| 650 | 4 | |a microRNA-374a | |
| 650 | 4 | |a myocardial injury | |
| 650 | 4 | |a severe acute pancreatitis | |
| 700 | 1 | |a Gu, Renlian |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Zhong |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Yanshuo |e verfasserin |4 aut | |
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