MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3
Introduction and objectives: Alcoholic hepatitis (AH) is characterized by high morbidity and mortality. MicroRNA-494-3p is possibly involved in the regulation of cancers, but its role in AH has been rarely studied. Materials and methods: AH mice model and primarily cultured mice hepatic stellate cel...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268121000041 |
| _version_ | 1818892601860816896 |
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| author | Hualong Li Lei Zhang Nan Cai Bing Zhang Shaomei Sun |
| author_facet | Hualong Li Lei Zhang Nan Cai Bing Zhang Shaomei Sun |
| author_sort | Hualong Li |
| collection | DOAJ |
| description | Introduction and objectives: Alcoholic hepatitis (AH) is characterized by high morbidity and mortality. MicroRNA-494-3p is possibly involved in the regulation of cancers, but its role in AH has been rarely studied. Materials and methods: AH mice model and primarily cultured mice hepatic stellate cells (HSCs) model were constructed. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed by ELISA. Expressions of miRNAs, HSC activation-related proteins and fibrosis-related protein were analyzed by qRT-PCR and Western blot. Cell counting kit, colony formation and flow cytometry assays were used to detect cell viability, proliferation and apoptosis, respectively. The relationship between TNF receptor-associated factor 3 (TRAF3) and miR-494-3p was predicted and verified by TargetScan and dual-luciferase assay, respectively. Results of the above experiments were verified by rescue experiments using TRAF3. Results: Liver damage and miRNA expression were observed in AH mice, and AST and ALT levels were increased in serum of AH mice. MiR-494-3p was reduced in AH liver tissues, and it decreased the levels of α-SMA and fibrosis-related proteins. HSCs were isolated, and activating HSCs or upregulating miR-494-3p had a regulatory effect on the levels of miR-494-3p, HSC activation-related proteins and fibrosis-related proteins as well as cell viability, proliferation and apoptosis. In addition, miR-494-3p targeted TRAF3 and inhibited TRAF3 expression, while overexpressed TRAF3 promoted TRAF3 expression and rescued the regulatory effect of miR-494-3p on the levels of related proteins as well as cell viability, proliferation and apoptosis. Conclusions: This study provided a novel mechanistic comprehension of the anti-fibrotic effect of miR-494-3p. |
| first_indexed | 2024-12-19T17:59:18Z |
| format | Article |
| id | doaj.art-22ef128b0f704a67b3a53ea05163500b |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-19T17:59:18Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-22ef128b0f704a67b3a53ea05163500b2022-12-21T20:11:44ZengElsevierAnnals of Hepatology1665-26812021-07-0123100305MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3Hualong Li0Lei Zhang1Nan Cai2Bing Zhang3Shaomei Sun4Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, 264100, ChinaCorresponding author at: Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, 717 Jinyu Street, Muping District, Yantai, Shandong Province, 264100, China.; Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, 264100, ChinaDepartment of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, 264100, ChinaDepartment of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, 264100, ChinaDepartment of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, 264100, ChinaIntroduction and objectives: Alcoholic hepatitis (AH) is characterized by high morbidity and mortality. MicroRNA-494-3p is possibly involved in the regulation of cancers, but its role in AH has been rarely studied. Materials and methods: AH mice model and primarily cultured mice hepatic stellate cells (HSCs) model were constructed. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed by ELISA. Expressions of miRNAs, HSC activation-related proteins and fibrosis-related protein were analyzed by qRT-PCR and Western blot. Cell counting kit, colony formation and flow cytometry assays were used to detect cell viability, proliferation and apoptosis, respectively. The relationship between TNF receptor-associated factor 3 (TRAF3) and miR-494-3p was predicted and verified by TargetScan and dual-luciferase assay, respectively. Results of the above experiments were verified by rescue experiments using TRAF3. Results: Liver damage and miRNA expression were observed in AH mice, and AST and ALT levels were increased in serum of AH mice. MiR-494-3p was reduced in AH liver tissues, and it decreased the levels of α-SMA and fibrosis-related proteins. HSCs were isolated, and activating HSCs or upregulating miR-494-3p had a regulatory effect on the levels of miR-494-3p, HSC activation-related proteins and fibrosis-related proteins as well as cell viability, proliferation and apoptosis. In addition, miR-494-3p targeted TRAF3 and inhibited TRAF3 expression, while overexpressed TRAF3 promoted TRAF3 expression and rescued the regulatory effect of miR-494-3p on the levels of related proteins as well as cell viability, proliferation and apoptosis. Conclusions: This study provided a novel mechanistic comprehension of the anti-fibrotic effect of miR-494-3p.http://www.sciencedirect.com/science/article/pii/S1665268121000041Alcoholic hepatitisHepatic stellate cellmiR-494-3pTNF receptor-associated factor 3 |
| spellingShingle | Hualong Li Lei Zhang Nan Cai Bing Zhang Shaomei Sun MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3 Annals of Hepatology Alcoholic hepatitis Hepatic stellate cell miR-494-3p TNF receptor-associated factor 3 |
| title | MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3 |
| title_full | MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3 |
| title_fullStr | MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3 |
| title_full_unstemmed | MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3 |
| title_short | MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3 |
| title_sort | microrna 494 3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting traf3 |
| topic | Alcoholic hepatitis Hepatic stellate cell miR-494-3p TNF receptor-associated factor 3 |
| url | http://www.sciencedirect.com/science/article/pii/S1665268121000041 |
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