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

文献类型：期刊论文

作者Li W(李旺); Li PW(李培文); Li N(李宁); Du Y(杜宇); Lv SQ(吕守芹); Elad, David2; Long M(龙勉)
刊名AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY ; 3
出版日期2020-03
卷号320页码:G272-G282
关键词hepatocytes liver fibrosis matrix stiffness shear flow three-dimensional liver sinusoidal model
ISSN号0193-1857
DOI10.1152/ajpgi.00379.2019
英文摘要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.
学科主题Gastroenterology & Hepatology ; Physiology
分类号二类
语种英语
WOS记录号WOS:000726767600005
资助机构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]
其他责任者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.
源URL[http://dspace.imech.ac.cn/handle/311007/90234]  
专题力学研究所_国家微重力实验室
作者单位1.Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Tel Aviv, Israel
2.Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, 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, Inst Mech, Beijing, Peoples R China
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, 3,2020,320: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,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(2020):G272-G282.

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来源：力学研究所

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