FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration
Abstract Liver regeneration is critical for maintaining whole‐body homeostasis, especially under exposure to deadly chemical toxins. Understanding the molecular mechanisms underlying liver repair is critical for the development of intervention strategies to treat liver diseases. In this study, ubiqu...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408724 |
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| author | Nanfei Yang Qiang Tian Zhenli Lei Shuxin Wang Nan Cheng Zhen Wang Xianqin Jiang Xuqun Zheng Wenjing Xu Minyan Ye Longwei Zhao Meiyun Wen Jianlou Niu Weijian Sun Pingping Shen Zhifeng Huang Xiaokun Li |
| author_facet | Nanfei Yang Qiang Tian Zhenli Lei Shuxin Wang Nan Cheng Zhen Wang Xianqin Jiang Xuqun Zheng Wenjing Xu Minyan Ye Longwei Zhao Meiyun Wen Jianlou Niu Weijian Sun Pingping Shen Zhifeng Huang Xiaokun Li |
| author_sort | Nanfei Yang |
| collection | DOAJ |
| description | Abstract Liver regeneration is critical for maintaining whole‐body homeostasis, especially under exposure to deadly chemical toxins. Understanding the molecular mechanisms underlying liver repair is critical for the development of intervention strategies to treat liver diseases. In this study, ubiquitin‐specific Proteases 42 (USP42) is identified as a novel deubiquitinases (DUB) of peroxisome proliferators‐activated receptor γ (PPARγ) in hepatocytes. This DUB interacted, deubiquitinated, and stabilized PPARγ, and increased PPARγ targeted proliferative and antioxidative gene expressions, which protects the liver from carbon tetrachloride (CCL4) induced oxidative injury and promotes liver regeneration. In addition, fibroblast growth factor 2 (FGF2) initiated USP42 expression and enhanced the interaction between USP42 and PPARγ during the liver regeneration process. Moreover, the PPARγ full agonist, rosiglitazone (RSG), possesses the ability to further reinforce the USP42‐PPARγ interplay, which enlightens to construct of an extracellular vesicle‐based targeting strategy to activate the liver USP42‐PPARγ axis and promote liver regeneration. In summary, the work uncovers the importance of USP42‐PPARγ axis‐mediated liver tissue homeostasis and provides a promising regimen to target this protein‐protein interplay for liver regeneration. |
| format | Article |
| id | doaj-art-ce418aec99014ebeb5683694e252e826 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-ce418aec99014ebeb5683694e252e8262025-08-20T02:08:14ZengWileyAdvanced Science2198-38442025-05-011218n/an/a10.1002/advs.202408724FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes RegenerationNanfei Yang0Qiang Tian1Zhenli Lei2Shuxin Wang3Nan Cheng4Zhen Wang5Xianqin Jiang6Xuqun Zheng7Wenjing Xu8Minyan Ye9Longwei Zhao10Meiyun Wen11Jianlou Niu12Weijian Sun13Pingping Shen14Zhifeng Huang15Xiaokun Li16Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaDepartment of Colorectal Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325027 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaSchool of Integrative Medicine Nanjing University of Chinese Medicine Nanjing 210023 ChinaState Key Laboratory of Pharmaceutical Biotechnology and Clinical Stem Cell Center The Affiliated Drum Tower Hospital of Nanjing University Medical School School of Life Sciences Nanjing University Nanjing 210023 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaDepartment of Pharmacology School of Basic Medical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaDepartment of Pharmacology School of Basic Medical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaDepartment of Colorectal Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325027 ChinaDepartment of Colorectal Surgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325027 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health) State Key Laboratory of Macromolecular Drugs and Large‐scale Preparation School of Pharmaceutical Sciences Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaAbstract Liver regeneration is critical for maintaining whole‐body homeostasis, especially under exposure to deadly chemical toxins. Understanding the molecular mechanisms underlying liver repair is critical for the development of intervention strategies to treat liver diseases. In this study, ubiquitin‐specific Proteases 42 (USP42) is identified as a novel deubiquitinases (DUB) of peroxisome proliferators‐activated receptor γ (PPARγ) in hepatocytes. This DUB interacted, deubiquitinated, and stabilized PPARγ, and increased PPARγ targeted proliferative and antioxidative gene expressions, which protects the liver from carbon tetrachloride (CCL4) induced oxidative injury and promotes liver regeneration. In addition, fibroblast growth factor 2 (FGF2) initiated USP42 expression and enhanced the interaction between USP42 and PPARγ during the liver regeneration process. Moreover, the PPARγ full agonist, rosiglitazone (RSG), possesses the ability to further reinforce the USP42‐PPARγ interplay, which enlightens to construct of an extracellular vesicle‐based targeting strategy to activate the liver USP42‐PPARγ axis and promote liver regeneration. In summary, the work uncovers the importance of USP42‐PPARγ axis‐mediated liver tissue homeostasis and provides a promising regimen to target this protein‐protein interplay for liver regeneration.https://doi.org/10.1002/advs.202408724FGF2liver regenerationnano‐therapyPPARγredox balanceUSP42 |
| spellingShingle | Nanfei Yang Qiang Tian Zhenli Lei Shuxin Wang Nan Cheng Zhen Wang Xianqin Jiang Xuqun Zheng Wenjing Xu Minyan Ye Longwei Zhao Meiyun Wen Jianlou Niu Weijian Sun Pingping Shen Zhifeng Huang Xiaokun Li FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration Advanced Science FGF2 liver regeneration nano‐therapy PPARγ redox balance USP42 |
| title | FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration |
| title_full | FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration |
| title_fullStr | FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration |
| title_full_unstemmed | FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration |
| title_short | FGF2 Mediated USP42‐PPARγ Axis Activation Ameliorates Liver Oxidative Damage and Promotes Regeneration |
| title_sort | fgf2 mediated usp42 pparγ axis activation ameliorates liver oxidative damage and promotes regeneration |
| topic | FGF2 liver regeneration nano‐therapy PPARγ redox balance USP42 |
| url | https://doi.org/10.1002/advs.202408724 |
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