| Direct mechanical exposure initiates hepatocyte proliferation |
| Li, Wang ; Wu Y(武亿); Hu, Wenhui; Zhou J(周瑾); Shu XY(舒芯钰); Zhang XY(张晓宇); Zhang, Ziliang; Wu, Huan; Du, Yu; Lv DY(吕东媛); Lv SQ(吕守芹); Li N(李宁); Long M(龙勉)
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| Corresponding Author | Li, Ning(lining_1@imech.ac.cn)
; Long, Mian(mlong@imech.ac.cn)
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| Source Publication | JHEP REPORTS
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| 2023-12-01
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| Volume | 5Issue:12Pages:13 |
| Abstract | Background & Aims: Liver paracrine signaling from liver sinusoid endothelial cells to hepatocytes in response to mechanical stimuli is crucial in highly coordinated liver regeneration. Interstitial flow through the fenestrated endothelium inside the space of Disse potentiates the role of direct exposure of hepatocytes to fluid flow in the immediate regenerative responses after partial hepatectomy, but the underlying mechanisms remain unclear.Methods: Mouse liver perfusion was used to identify the effects of interstitial flow on hepatocyte proliferation ex vivo. Isolated hepatocytes were further exposed to varied shear stresses directly in vitro. Knockdown and/or inhibition of mechanosensitive proteins were used to unravel the signaling pathways responsible for cell proliferation.Results: An increased interstitial flow was visualized and hepatocytes' regenerative response was demonstrated experimentally by ex vivo perfusion of mouse livers. In vitro measurements also showed that fluid flow initiated hepatocyte pro-liferation in a duration-and amplitude-dependent manner. Mechanistically, flow enhanced 01 integrin expression and nuclear translocation of YAP (yes-associated protein), via the Hippo pathway, to stimulate hepatocytes to re-enter the cell cycle.Conclusions: Hepatocyte proliferation was initiated after direct exposure to interstitial flow ex vivo or shear stress in vitro, which provides new insights into the contributions of mechanical forces to liver regeneration. Impact and implications: By using both ex vivo liver perfusion and in vitro flow exposure tests, we identified the roles of interstitial flow in the space of Disse in stimulating hepatocytes to re-enter the cell cycle. We found an increase in shear flow -induced hepatocyte proliferation via 01 integrin-YAP mechanotransductive pathways. This serves as a useful model to potentiate hepatocyte expansion in vitro using mechanical forces.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keyword | Mechanotransduction
FAK
hepatic sinusoid chip
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| DOI | 10.1016/j.jhepr.2023.100905
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| Indexed By | SCI
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| Language | 英语
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| WOS ID | WOS:001110520000001
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| WOS Keyword | CYCLIN D1
; LIVER
; REGENERATION
; EXPRESSION
; PHYSIOLOGY
; CELLS
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| WOS Research Area | Gastroenterology & Hepatology
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| WOS Subject | Gastroenterology & Hepatology
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| Funding Project | National Natural Science Foundation of China[32130061]
; National Natural Science Foundation of China[32271366]
; National Natural Science Foundation of China[32101056]
; National Key R&D Program of China[2021YFA0719300]
; China Manned Space Flight Technology Project Chinese Space Station Experiment Project[YYW- T0901EXP0701]
; Key Research Program of Chinese Academy of Sciences[GJJSTU20220002]
; Key Research Program of Chinese Academy of Sciences[ZDBS-ZRKJZ-TLC0 02]
; Scientific Instrument Developing Project of Chinese Academy of Sciences[GJJSTU20220002]
; Scientific Instrument Developing Project of Chinese Academy of Sciences[ZDBS-ZRKJZ-TLC0 02]
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| Funding Organization | National Natural Science Foundation of China
; National Key R&D Program of China
; China Manned Space Flight Technology Project Chinese Space Station Experiment Project
; Key Research Program of Chinese Academy of Sciences
; Scientific Instrument Developing Project of Chinese Academy of Sciences
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| Classification | 一类
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| Ranking | 1
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| Contributor | Li, Ning
; Long, Mian
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| Citation statistics |
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| Document Type | 期刊论文
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| Identifier | http://dspace.imech.ac.cn/handle/311007/93531
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| Collection | 微重力重点实验室
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Recommended Citation
GB/T 7714 |
Li, Wang,Wu Y,Hu, Wenhui,et al. Direct mechanical exposure initiates hepatocyte proliferation[J]. JHEP REPORTS,2023,5,12,:13.Rp_Au:Li, Ning, Long, Mian
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| APA |
Li, Wang.,武亿.,Hu, Wenhui.,周瑾.,舒芯钰.,...&龙勉.(2023).Direct mechanical exposure initiates hepatocyte proliferation.JHEP REPORTS,5(12),13.
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| MLA |
Li, Wang,et al."Direct mechanical exposure initiates hepatocyte proliferation".JHEP REPORTS 5.12(2023):13.
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