miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4
Aims. Fibroblast growth factor receptor 4 (FGFR4) is a key mediator that protects the liver from chronic injury. MicroRNA-7 (miR-7) is a tumor suppressor and associated with lipid homeostasis in the liver. This study was designed to examine the role of the miR-7-5p/FGFR4 axis in liver fibrogenesis....
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2020/5346573 |
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| _version_ | 1832560159685083136 |
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| author | Shuxia Tian Min Chen Bing Wang Yonglong Han Haonan Shang Junming Chen |
| author_facet | Shuxia Tian Min Chen Bing Wang Yonglong Han Haonan Shang Junming Chen |
| author_sort | Shuxia Tian |
| collection | DOAJ |
| description | Aims. Fibroblast growth factor receptor 4 (FGFR4) is a key mediator that protects the liver from chronic injury. MicroRNA-7 (miR-7) is a tumor suppressor and associated with lipid homeostasis in the liver. This study was designed to examine the role of the miR-7-5p/FGFR4 axis in liver fibrogenesis. Methods. TargetScan was employed to predict microRNAs that targeted FGFR4 on the 3′-untranslated region (3′-UTR). miR-7-5p and FGFR4 expression in pathological liver tissues and LX-2 cells was determined using qRT-PCR and an immunoblotting assay. A dual-luciferase assay was conducted to validate the target prediction. A Cell Counting Lit-8 assay was performed to assess the proliferation ability of LX-2 cells. Hydroxyproline content in LX-2 cells was measured using a hydroxyproline assay. The expression of hepatic stellate cell (HSC) activation markers was examined using qRT-PCR and an immunoblotting assay. Results. FGFR4 was a putative target of miR-7-5p. In LX-2 cells, miR-7-5p targeted FGFR4 by binding to 3′-UTR. FGFR4 was downregulated, but miR-7-5p was markedly enhanced in the liver samples as the degree of liver fibrosis rose. miR-7-5p was negatively associated with FGFR4 expression in liver tissues. The miR-7-5p inhibitor blocked the lipopolysaccharide-induced proliferation and activation of LX-2 cells, and FGFR4 overexpression inhibited LX-2 cell proliferation and activation triggered by miR-7-5p. Conclusion. miR-7-5p promotes HSC proliferation and activation by downregulating FGFR4. |
| format | Article |
| id | doaj-art-1475306465294abb81210fb169bf175e |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-1475306465294abb81210fb169bf175e2025-02-03T01:28:10ZengWileyGastroenterology Research and Practice1687-61211687-630X2020-01-01202010.1155/2020/53465735346573miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4Shuxia Tian0Min Chen1Bing Wang2Yonglong Han3Haonan Shang4Junming Chen5Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, ChinaShanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, ChinaShanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, ChinaAims. Fibroblast growth factor receptor 4 (FGFR4) is a key mediator that protects the liver from chronic injury. MicroRNA-7 (miR-7) is a tumor suppressor and associated with lipid homeostasis in the liver. This study was designed to examine the role of the miR-7-5p/FGFR4 axis in liver fibrogenesis. Methods. TargetScan was employed to predict microRNAs that targeted FGFR4 on the 3′-untranslated region (3′-UTR). miR-7-5p and FGFR4 expression in pathological liver tissues and LX-2 cells was determined using qRT-PCR and an immunoblotting assay. A dual-luciferase assay was conducted to validate the target prediction. A Cell Counting Lit-8 assay was performed to assess the proliferation ability of LX-2 cells. Hydroxyproline content in LX-2 cells was measured using a hydroxyproline assay. The expression of hepatic stellate cell (HSC) activation markers was examined using qRT-PCR and an immunoblotting assay. Results. FGFR4 was a putative target of miR-7-5p. In LX-2 cells, miR-7-5p targeted FGFR4 by binding to 3′-UTR. FGFR4 was downregulated, but miR-7-5p was markedly enhanced in the liver samples as the degree of liver fibrosis rose. miR-7-5p was negatively associated with FGFR4 expression in liver tissues. The miR-7-5p inhibitor blocked the lipopolysaccharide-induced proliferation and activation of LX-2 cells, and FGFR4 overexpression inhibited LX-2 cell proliferation and activation triggered by miR-7-5p. Conclusion. miR-7-5p promotes HSC proliferation and activation by downregulating FGFR4.http://dx.doi.org/10.1155/2020/5346573 |
| spellingShingle | Shuxia Tian Min Chen Bing Wang Yonglong Han Haonan Shang Junming Chen miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4 Gastroenterology Research and Practice |
| title | miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4 |
| title_full | miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4 |
| title_fullStr | miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4 |
| title_full_unstemmed | miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4 |
| title_short | miR-7-5p Promotes Hepatic Stellate Cell Activation by Targeting Fibroblast Growth Factor Receptor 4 |
| title_sort | mir 7 5p promotes hepatic stellate cell activation by targeting fibroblast growth factor receptor 4 |
| url | http://dx.doi.org/10.1155/2020/5346573 |
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