| Stretch-induced hepatic endothelial mechanocrine promotes hepatocyte proliferation | |
Wu Y(武亿); Li LD(李林达); Li, Wang ; Li N(李宁); Zhang XY(张晓宇); Zheng L(郑璐); Zhong SY(钟绍宇); Lv SQ(吕守芹); Shu XY(舒芯钰); Zhou J(周瑾); Ai, Ding; Gao, Ming; Liu, Sijin; Lv DY(吕东媛); Long M(龙勉)
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| Source Publication | HEPATOLOGY
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| 2024-09 | |
| ISSN | 0270-9139 |
| Abstract | Background and Aims:Partial hepatectomy-induced liver regeneration causes the increase in relative blood flow rate within the liver, which dilates hepatic sinusoids and applies mechanical stretch on liver sinusoidal endothelial cells (LSECs). Heparin-binding EGF-like growth factor is a crucial growth factor during liver regeneration. We aimed to investigate whether this sinusoidal dilation-induced stretch promotes HB-EGF secretion in LSECs and what the related molecular mechanism is. Approach and Results: In vivo partial hepatectomy, ex vivo liver perfusion, and in vitro LSEC mechanical stretch were applied to detect HB-EGF expression in LSECs and hepatocyte proliferation. Knockdown or inhibition of mechanosensitive proteins was used to unravel the molecular mechanism in response to stretch. This stretch triggers amplitude-dependent and duration-dependent HB-EGF upregulation in LSECs, which is mediated by Yes-associated protein (YAP) nuclear translocation and binding to TEA domain family. This YAP translocation is achieved in 2 ways: On one hand, F-actin polymerization-mediated expansion of nuclear pores promotes YAP entry into nucleus passively. On the other hand, F-actin polymerization upregulates the expression of BAG family molecular chaperone regulator 3, which binds with YAP to enter the nucleus cooperatively. In this process, beta 1-integrin serves as a target mechanosensory in stretch-induced signaling pathways. This HB-EGF secretion-promoted liver regeneration after 2/3 partial hepatectomy is attenuated in endothelial cell-specific Yap1-deficient mice. Conclusions:Our findings indicate that mechanical stretch-induced HB-EGF upregulation in LSECs through YAP translocation can promote hepatocyte proliferation during liver regeneration through a mechanocrine manner, which deepens the understanding of the mechanical-biological coupling in liver regeneration. |
| Keyword | HB-EGF liver regeneration liver sinusoidal endothelial cell mechanotransduction mechanical stretch |
| DOI | 10.1097/HEP.0000000000001082 |
| Indexed By | SCI |
| Language | 英语 |
| WOS ID | WOS:001329010700001 |
| WOS Research Area | Gastroenterology & Hepatology |
| WOS Subject | Gastroenterology & Hepatology |
| Funding Organization | National Key Research and Development Program of China {2021YFA0719302] ; National Natural Science Foundation of China {32130061, T2394514, 32371376] ; Scientific Instrument Developing Project of the Chinese Academy of Sciences {GJJSTU20220002] |
| Classification | 一类 |
| Ranking | 1 |
| Contributor | Lü DY ; Long M |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/97194 |
| Collection | 微重力重点实验室 |
| Affiliation | 1.【Wu, Yi & Li, Linda & Li, Wang & Li, Ning & Zhang, Xiaoyu & Zheng, Lu & Zhong, Shaoyu & Lue, Shouqin & Shu, Xinyu & Zhou, Jin & Lue, Dongyuan & Long, Mian】 Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing Key Lab Engn Construct & Mechanobiol, 15 Beisihuanxi Rd, Beijing 100190, Peoples R China 2.【Wu, Yi & Li, Linda & Li, Wang & Li, Ning & Zhang, Xiaoyu & Zheng, Lu & Zhong, Shaoyu & Lue, Shouqin & Shu, Xinyu & Zhou, Jin & Lue, Dongyuan & Long, Mian】 Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, 15 Beisihuanxi Rd, Beijing 100190, Peoples R China 3.【Wu, Yi & Li, Wang & Li, Ning & Zhang, Xiaoyu & Zheng, Lu & Lue, Shouqin & Shu, Xinyu & Zhou, Jin & Gao, Ming & Liu, Sijin & Lue, Dongyuan & Long, Mian】 Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China 4.【Ai, Ding】 Tianjin Med Univ, Dept Physiol & Pathophysiol, Tianjin, Peoples R China 5.【Gao, Ming & Liu, Sijin】 Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing, Peoples R China |
| Recommended Citation GB/T 7714 | Wu Y,Li LD,Li, Wang,et al. Stretch-induced hepatic endothelial mechanocrine promotes hepatocyte proliferation[J]. HEPATOLOGY,2024.Rp_Au:Lü DY, Long M |
| APA | 武亿.,李林达.,Li, Wang.,李宁.,张晓宇.,...&龙勉.(2024).Stretch-induced hepatic endothelial mechanocrine promotes hepatocyte proliferation.HEPATOLOGY. |
| MLA | 武亿,et al."Stretch-induced hepatic endothelial mechanocrine promotes hepatocyte proliferation".HEPATOLOGY (2024). |
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