| 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, David4; Long M(龙勉)
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| Source Publication | AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
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| 2020-03 | |
| Volume | 320Issue:3Pages:G272-G282 |
| ISSN | 0193-1857 |
| Abstract | 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. |
| Keyword | hepatocytes liver fibrosis matrix stiffness shear flow three-dimensional liver sinusoidal model |
| Subject Area | Gastroenterology & Hepatology ; Physiology |
| DOI | 10.1152/ajpgi.00379.2019 |
| Indexed By | SCI |
| Language | 英语 |
| WOS ID | WOS:000726767600005 |
| Funding Organization | 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] |
| Classification | 二类 |
| Ranking | 1 |
| Contributor | 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. |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/90234 |
| Collection | 微重力重点实验室 |
| Affiliation | 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 |
| Recommended Citation 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.Rp_Au: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. |
| 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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| FA009.pdf（2812KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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