Direct mechanical exposure initiates hepatocyte proliferation

doi:10.1016/j.jhepr.2023.100905

	Direct mechanical exposure initiates hepatocyte proliferation
	Li, Wang 3,4,5; Wu, Yi 3,4,5; Hu, Wenhui 4,5; Zhou, Jin 4,5; Shu, Xinyu 3,4,5; Zhang, Xiaoyu 3,4,5; Zhang, Ziliang 2,4,5; Wu, Huan 4,5; Du, Yu 4,5; Lu, Dongyuan 3,4,5
刊名	JHEP REPORTS
	2023-12-01
卷号	5 期号:12 页码:13
关键词	Mechanotransduction FAK hepatic sinusoid chip
DOI	10.1016/j.jhepr.2023.100905
通讯作者	Li, Ning(lining_1@imech.ac.cn) ; Long, Mian(mlong@imech.ac.cn)
英文摘要	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/).
资助项目	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]
WOS关键词	CYCLIN D1 ; LIVER ; REGENERATION ; EXPRESSION ; PHYSIOLOGY ; CELLS
WOS研究方向	Gastroenterology & Hepatology
语种	英语
WOS记录号	WOS:001110520000001
资助机构	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
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/93530]
专题	力学研究所_国家微重力实验室
通讯作者	Li, Ning; Long, Mian
作者单位	1.Chinese Acad Sci, Inst Mech, Beijing 100190, Peoples R China 2.Shandong First Med Univ & Shandong Acad Med Sci, Med Sci & Technol Innovat Ctr, Jinan, Peoples R China 3.Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China 4.Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing, Peoples R China 5.Chinese Acad Sci, Ctr Biomech & Bioengn, Beijing Key Lab Engn Construct & Mechanobiol, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Li, Wang,Wu, Yi,Hu, Wenhui,et al. Direct mechanical exposure initiates hepatocyte proliferation[J]. JHEP REPORTS,2023,5(12):13.
APA	Li, Wang.,Wu, Yi.,Hu, Wenhui.,Zhou, Jin.,Shu, Xinyu.,...&Long, Mian.(2023).Direct mechanical exposure initiates hepatocyte proliferation.JHEP REPORTS,5(12),13.
MLA	Li, Wang,et al."Direct mechanical exposure initiates hepatocyte proliferation".JHEP REPORTS 5.12(2023):13.