Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model

doi:10.1152/ajpgi.00379.2019

IMECH-IR > 微重力重点实验室

	Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model
	Li W(李旺); Li PW(李培文); Li N(李宁); Du Y(杜宇); Lv SQ(吕守芹); Elad, David 4; Long M(龙勉)
发表期刊	AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
	2020-03
卷号	320 期号:3 页码:G272-G282
ISSN	0193-1857
摘要	Extracellular matrix (ECM) rigidity has important effects on cell behaviors and increases sharply in liver fibrosis and cirrhosis. Hepatic blood flow is essential in maintaining hepatocytes' (HCs) functions. However, it is still unclear how matrix stiffness and shear stresses orchestrate HC phenotype in concert. A fibrotic three-dimensional (3-D) liver sinusoidal model is constructed using a porous membrane sandwiched between two polydimethylsiloxane (PDMS) layers with respective flow channels. The HCs are cultured in collagen gels of various stiffnesses in the lower channel, whereas the upper channel is pre-seeded with liver sinusoidal endothelial cells (LSECs) and accessible to shear flow. The results reveal that HCs cultured within stiffer matrices exhibit reduced albumin production and cytochrome P450 (CYP450) reductase expression. Low shear stresses enhance synthetic and metabolic functions of HC, whereas high shear stresses lead to the loss of HC phenotype. Furthermore, both mechanical factors regulate HC functions by complementing each other. These observations are likely attributed to mechanically induced mass transport or key signaling molecule of hepatocyte nuclear factor 4 alpha (HNF4 alpha). The present study results provide an insight into understanding the mechanisms of HC dysfunction in liver fibrosis and cirrhosis, especially from the viewpoint of matrix stiffness and blood flow. NEW & NOTEWORTHY A fibrotic three-dimensional (3-D) liver sinusoidal model was constructed to mimic different stages of liver fibrosis in vivo and to explore the cooperative effects of matrix stiffness and shear stresses on hepatocyte (HC) functions. Mechanically induced alterations of mass transport mainly contributed to HC functions via typical mechanosensitive signaling.
关键词	hepatocytes liver fibrosis matrix stiffness shear flow three-dimensional liver sinusoidal model
学科领域	Gastroenterology & Hepatology ; Physiology
DOI	10.1152/ajpgi.00379.2019
收录类别	SCI
语种	英语
WOS记录号	WOS:000726767600005
项目资助者	National Natural Science Foundation of China [91642203, 31627804, 31661143044, 31870930] ; Strategic Priority Research Program, Frontier Science Key Project ; Scientific Instrument Developing Project of Chinese Academy of Sciences [QYZDJ-SSW-JSC018, XDB22040101, GJJSTU20190005]
论文分区	二类
力学所作者排名	1
RpAuthor	Long, MA (corresponding author), Chinese Acad Sci, Ctr Biomech & Bioengn, Inst Mech, Beijing, Peoples R China. ; Long, MA (corresponding author), Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing, Peoples R China. ; Long, MA (corresponding author), Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing, Peoples R China. ; Long, MA (corresponding author), Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China.
引用统计	被引频次：16[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://dspace.imech.ac.cn/handle/311007/90234
专题	微重力重点实验室
作者单位	1.Chinese Acad Sci, Ctr Biomech & Bioengn, Inst Mech, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing, Peoples R China 3.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing, Peoples R China 4.Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China 5.Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Tel Aviv, Israel
推荐引用方式 GB/T 7714	Li W,Li PW,Li N,et al. Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model[J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,2020,320,3,:G272-G282.
APA	李旺.,李培文.,李宁.,杜宇.,吕守芹.,...&龙勉.(2020).Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model.AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,320(3),G272-G282.
MLA	李旺,et al."Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model".AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY 320.3(2020):G272-G282.

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