microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in mice
Objective: This study aimed to determine the roles of microRNA (miR)-122 in the activation of hepatic stellate cells (HSCs) and liver cirrhosis. Methods: Rat primary HSCs were incubated with transforming growth factor-beta (TGF-β), during which miR-122 and EphB2 expression was measured. miR-122 mimi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268122000424 |
| _version_ | 1811329885809934336 |
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| author | Jing Ma Qiqian Zhao Mengxuan Chen Weihang Wang Bo He Yongfang Jiang Yi Li |
| author_facet | Jing Ma Qiqian Zhao Mengxuan Chen Weihang Wang Bo He Yongfang Jiang Yi Li |
| author_sort | Jing Ma |
| collection | DOAJ |
| description | Objective: This study aimed to determine the roles of microRNA (miR)-122 in the activation of hepatic stellate cells (HSCs) and liver cirrhosis. Methods: Rat primary HSCs were incubated with transforming growth factor-beta (TGF-β), during which miR-122 and EphB2 expression was measured. miR-122 mimic and/or pcDNA3.1 EphB2 was transfected into TGF-β-induced HSCs. A mouse model of liver cirrhosis was established via an intraperitoneal injection of carbon tetrachloride (CCl4), followed by the injection of miR-122 agomir. Levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured. Fibronectin (FN), alpha smooth muscle actin (α-SMA), Collagen I, miR-122, and EphB2 expression was evaluated in liver tissues and HSCs. Cell proliferation was measured using CCK-8 assay. Interactions between miR-122 and EphB2 were assessed using dual luciferase reporter assay. Results: miR-122 (0.15-fold) was downregulated and EphB2 (mRNA: 5.06-fold; protein: 2.35-fold) was upregulated after TGF-β induction of HSCs. Overexpressed miR-122 decreased proliferation and EphB2 (mRNA: 0.46-fold; protein: 0.62-fold), FN (mRNA: 0.45-fold; protein: 0.64-fold), α-SMA (mRNA: 0.48-fold; protein: 0.51-fold), and Collagen I (mRNA: 0.44-fold; protein: 0.51-fold) expression in HSCs, which was abrogated by EphB2 upregulation. miR-122 expression was reduced by 0.21-fold and serum ALT and AST levels were enhanced in mice following 8-week CCl4 induction along with increased expression of FN, α-SMA, and Collagen I in liver tissues, which was blocked by miR-122 overexpression. Moreover, EphB2 was a target gene of miR-122. Conclusion: miR-122 curtails HSC proliferation and activation by targeting EphB2 and suppresses liver cirrhosis in mice. |
| first_indexed | 2024-04-13T15:51:51Z |
| format | Article |
| id | doaj.art-6317058db7b246caa5890fbeaed245d0 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-04-13T15:51:51Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-6317058db7b246caa5890fbeaed245d02022-12-22T02:40:49ZengElsevierAnnals of Hepatology1665-26812022-07-01274100700microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in miceJing Ma0Qiqian Zhao1Mengxuan Chen2Weihang Wang3Bo He4Yongfang Jiang5Yi Li6Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. ChinaDepartment of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. ChinaDepartment of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. ChinaDepartment of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. ChinaDepartment of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. ChinaDepartment of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. ChinaCorresponding author.; Department of Infectious Diseases, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. ChinaObjective: This study aimed to determine the roles of microRNA (miR)-122 in the activation of hepatic stellate cells (HSCs) and liver cirrhosis. Methods: Rat primary HSCs were incubated with transforming growth factor-beta (TGF-β), during which miR-122 and EphB2 expression was measured. miR-122 mimic and/or pcDNA3.1 EphB2 was transfected into TGF-β-induced HSCs. A mouse model of liver cirrhosis was established via an intraperitoneal injection of carbon tetrachloride (CCl4), followed by the injection of miR-122 agomir. Levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured. Fibronectin (FN), alpha smooth muscle actin (α-SMA), Collagen I, miR-122, and EphB2 expression was evaluated in liver tissues and HSCs. Cell proliferation was measured using CCK-8 assay. Interactions between miR-122 and EphB2 were assessed using dual luciferase reporter assay. Results: miR-122 (0.15-fold) was downregulated and EphB2 (mRNA: 5.06-fold; protein: 2.35-fold) was upregulated after TGF-β induction of HSCs. Overexpressed miR-122 decreased proliferation and EphB2 (mRNA: 0.46-fold; protein: 0.62-fold), FN (mRNA: 0.45-fold; protein: 0.64-fold), α-SMA (mRNA: 0.48-fold; protein: 0.51-fold), and Collagen I (mRNA: 0.44-fold; protein: 0.51-fold) expression in HSCs, which was abrogated by EphB2 upregulation. miR-122 expression was reduced by 0.21-fold and serum ALT and AST levels were enhanced in mice following 8-week CCl4 induction along with increased expression of FN, α-SMA, and Collagen I in liver tissues, which was blocked by miR-122 overexpression. Moreover, EphB2 was a target gene of miR-122. Conclusion: miR-122 curtails HSC proliferation and activation by targeting EphB2 and suppresses liver cirrhosis in mice.http://www.sciencedirect.com/science/article/pii/S1665268122000424Hepatic stellate cellCirrhosismicroRNA-122EphB2Activation |
| spellingShingle | Jing Ma Qiqian Zhao Mengxuan Chen Weihang Wang Bo He Yongfang Jiang Yi Li microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in mice Annals of Hepatology Hepatic stellate cell Cirrhosis microRNA-122 EphB2 Activation |
| title | microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in mice |
| title_full | microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in mice |
| title_fullStr | microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in mice |
| title_full_unstemmed | microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in mice |
| title_short | microRNA-122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride-induced liver cirrhosis in mice |
| title_sort | microrna 122 inhibits hepatic stellate cell proliferation and activation in vitro and represses carbon tetrachloride induced liver cirrhosis in mice |
| topic | Hepatic stellate cell Cirrhosis microRNA-122 EphB2 Activation |
| url | http://www.sciencedirect.com/science/article/pii/S1665268122000424 |
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