TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis
Transforming growth factor-beta 1 (TGF-β1) plays a central role in hepatic progenitor cells- (HPCs-) mediated liver repair and fibrosis. However, different effects of TGF-β1 on progenitor cells have not been described. In this study, both in vitro (HPCs cocultured with hepatic stellate cells (HSCs)...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/1492694 |
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| author | Ai-Ting Yang Dou-Dou Hu Ping Wang Min Cong Tian-Hui Liu Dong Zhang Ya-Meng Sun Wen-Shan Zhao Ji-Dong Jia Hong You |
| author_facet | Ai-Ting Yang Dou-Dou Hu Ping Wang Min Cong Tian-Hui Liu Dong Zhang Ya-Meng Sun Wen-Shan Zhao Ji-Dong Jia Hong You |
| author_sort | Ai-Ting Yang |
| collection | DOAJ |
| description | Transforming growth factor-beta 1 (TGF-β1) plays a central role in hepatic progenitor cells- (HPCs-) mediated liver repair and fibrosis. However, different effects of TGF-β1 on progenitor cells have not been described. In this study, both in vitro (HPCs cocultured with hepatic stellate cells (HSCs) in transwells) and in vivo (CCl4-injured liver fibrosis rat) systems were used to evaluate the impacts. We found that HPCs pretreated with TGF-β1 for 12 hours inhibited the activation of HSCs, while sensitization for 48 hours increased the activation of HSCs. Consistent with these in vitro results, the in vivo fibrosis rat model showed the same time-dependent dual effect of TGF-β1. Regression of liver fibrosis as well as normalization of serum aminotransferase and albumin levels was detected in the rats transplanted with HPCs pretreated with TGF-β1 for 12 hours. In contrast, severe liver fibrosis and elevated collagen-1 levels were detected in the rats transplanted with HPCs pretreated with TGF-β1 for 48 hours. Furthermore, the TGF-β1-pretreated HPCs were shown to deactivate HSCs via enhancing SERPINE1 expression. Inhibition of SERPINE1 reversed the deactivation response in a dose-dependent manner. |
| format | Article |
| id | doaj-art-57f473d63a5b44818e8aab3fe9aad63e |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-57f473d63a5b44818e8aab3fe9aad63e2025-02-03T05:50:35ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/14926941492694TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver FibrosisAi-Ting Yang0Dou-Dou Hu1Ping Wang2Min Cong3Tian-Hui Liu4Dong Zhang5Ya-Meng Sun6Wen-Shan Zhao7Ji-Dong Jia8Hong You9Experimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaSecond Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaExperimental & Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Medicine Institute, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, ChinaTransforming growth factor-beta 1 (TGF-β1) plays a central role in hepatic progenitor cells- (HPCs-) mediated liver repair and fibrosis. However, different effects of TGF-β1 on progenitor cells have not been described. In this study, both in vitro (HPCs cocultured with hepatic stellate cells (HSCs) in transwells) and in vivo (CCl4-injured liver fibrosis rat) systems were used to evaluate the impacts. We found that HPCs pretreated with TGF-β1 for 12 hours inhibited the activation of HSCs, while sensitization for 48 hours increased the activation of HSCs. Consistent with these in vitro results, the in vivo fibrosis rat model showed the same time-dependent dual effect of TGF-β1. Regression of liver fibrosis as well as normalization of serum aminotransferase and albumin levels was detected in the rats transplanted with HPCs pretreated with TGF-β1 for 12 hours. In contrast, severe liver fibrosis and elevated collagen-1 levels were detected in the rats transplanted with HPCs pretreated with TGF-β1 for 48 hours. Furthermore, the TGF-β1-pretreated HPCs were shown to deactivate HSCs via enhancing SERPINE1 expression. Inhibition of SERPINE1 reversed the deactivation response in a dose-dependent manner.http://dx.doi.org/10.1155/2016/1492694 |
| spellingShingle | Ai-Ting Yang Dou-Dou Hu Ping Wang Min Cong Tian-Hui Liu Dong Zhang Ya-Meng Sun Wen-Shan Zhao Ji-Dong Jia Hong You TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis Stem Cells International |
| title | TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis |
| title_full | TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis |
| title_fullStr | TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis |
| title_full_unstemmed | TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis |
| title_short | TGF-β1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis |
| title_sort | tgf β1 induces the dual regulation of hepatic progenitor cells with both anti and proliver fibrosis |
| url | http://dx.doi.org/10.1155/2016/1492694 |
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