Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway
Abstract Given the widespread use of partial hepatectomy for treating various liver pathologies, understanding the mechanisms of liver regeneration is vital for enhancing liver resection and transplantation therapies. Here, we demonstrate the critical role of the serine protease Hepsin in promoting...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07357-1 |
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| author | Yu-Fei Tsai Mo-Chu Fang Chien-Hung Chen I-Shing Yu Chia-Tung Shun Mi-Hua Tao Cheng-Pu Sun Jean Lu Jin-Chuan Sheu Yu-Chen Hsu Shu-Wha Lin |
| author_facet | Yu-Fei Tsai Mo-Chu Fang Chien-Hung Chen I-Shing Yu Chia-Tung Shun Mi-Hua Tao Cheng-Pu Sun Jean Lu Jin-Chuan Sheu Yu-Chen Hsu Shu-Wha Lin |
| author_sort | Yu-Fei Tsai |
| collection | DOAJ |
| description | Abstract Given the widespread use of partial hepatectomy for treating various liver pathologies, understanding the mechanisms of liver regeneration is vital for enhancing liver resection and transplantation therapies. Here, we demonstrate the critical role of the serine protease Hepsin in promoting hepatocyte hypertrophy and proliferation. Under steady-state conditions, liver-specific overexpression of Hepsin in adult wild-type mice triggers hepatocyte hypertrophy and proliferation, significantly increasing liver size. This effect is predominantly driven by the catalytic activity of Hepsin, engaging the EGFR-Raf-MEK-ERK signaling pathway. Significantly, administering Hepsin substantially enhances hepatocyte proliferation and facilitates liver regeneration following a 70% partial hepatectomy. Crucially, the proliferation induced by Hepsin is a transient event, without leading to long-term adverse effects such as liver fibrosis or hepatocellular carcinoma, as evidenced by extensive observation. These results offer substantial potential for future clinical applications and translational research endeavors in the field of liver regeneration post-hepatectomy. |
| format | Article |
| id | doaj-art-0983f6cecc4843dba79d7399de51a483 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-0983f6cecc4843dba79d7399de51a4832024-12-22T12:41:57ZengNature PortfolioCommunications Biology2399-36422024-12-017111510.1038/s42003-024-07357-1Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathwayYu-Fei Tsai0Mo-Chu Fang1Chien-Hung Chen2I-Shing Yu3Chia-Tung Shun4Mi-Hua Tao5Cheng-Pu Sun6Jean Lu7Jin-Chuan Sheu8Yu-Chen Hsu9Shu-Wha Lin10Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityDepartment of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan UniversityLaboratory Animal Center, College of Medicine, National Taiwan UniversityDepartment and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityBiomedical Translation Research Center (BioTReC), Academia SinicaGenomics Research Center, Academia SinicaDepartment of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan UniversityAbstract Given the widespread use of partial hepatectomy for treating various liver pathologies, understanding the mechanisms of liver regeneration is vital for enhancing liver resection and transplantation therapies. Here, we demonstrate the critical role of the serine protease Hepsin in promoting hepatocyte hypertrophy and proliferation. Under steady-state conditions, liver-specific overexpression of Hepsin in adult wild-type mice triggers hepatocyte hypertrophy and proliferation, significantly increasing liver size. This effect is predominantly driven by the catalytic activity of Hepsin, engaging the EGFR-Raf-MEK-ERK signaling pathway. Significantly, administering Hepsin substantially enhances hepatocyte proliferation and facilitates liver regeneration following a 70% partial hepatectomy. Crucially, the proliferation induced by Hepsin is a transient event, without leading to long-term adverse effects such as liver fibrosis or hepatocellular carcinoma, as evidenced by extensive observation. These results offer substantial potential for future clinical applications and translational research endeavors in the field of liver regeneration post-hepatectomy.https://doi.org/10.1038/s42003-024-07357-1 |
| spellingShingle | Yu-Fei Tsai Mo-Chu Fang Chien-Hung Chen I-Shing Yu Chia-Tung Shun Mi-Hua Tao Cheng-Pu Sun Jean Lu Jin-Chuan Sheu Yu-Chen Hsu Shu-Wha Lin Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway Communications Biology |
| title | Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway |
| title_full | Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway |
| title_fullStr | Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway |
| title_full_unstemmed | Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway |
| title_short | Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway |
| title_sort | enhancement of adult liver regeneration in mice through the hepsin mediated epidermal growth factor receptor signaling pathway |
| url | https://doi.org/10.1038/s42003-024-07357-1 |
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