| FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration | |
Zhang XY(张晓宇)1,2,3; Li PW(李培文)1,2; Zhou J(周瑾)1,2; Zhang ZL(张子良)1,2,4; Wu H(吴欢)1,2; Shu XY(舒芯钰)1,2,3; Li W(李旺)1,2,3 ; Wu Y(武亿)1,2,3; Du Y(杜宇)1,2; Lv DY(吕东媛)1,2,3; Lv SQ(吕守芹)1,2,3; Li N(李宁)1,2,3,5; Long M(龙勉)1,2,3,5
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| Corresponding Author | Li, Ning([email protected]) ; Long, Mian([email protected]) |
| Source Publication | BIOMATERIALS
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| 2024-03-01 | |
| Volume | 305Pages:17 |
| ISSN | 0142-9612 |
| Abstract | Liver sinusoidal endothelial cells (LSECs) are highly specific endothelial cells which play an essential role in the maintenance of liver homeostasis. During the progression of liver fibrosis, matrix stiffening promotes LSEC defenestration, however, the underlying mechanotransduction mechanism remains poorly understood. Here, we applied stiffness-tunable hydrogels to assess the matrix stiffening-induced phenotypic changes in primary mouse LSECs. Results indicated that increased stiffness promoted LSEC defenestration through cytoskeletal reorganization. LSECs sensed the increased matrix stiffness via focal adhesion kinase (FAK), leading to the activation of p38-mitogen activated protein kinase activated protein kinase 2 (MK2) pathway, thereby inducing actin remodeling via LIM Kinase 1 (LIMK1) and Cofilin. Interestingly, inhibition of FAK or p38-MK2 pathway was able to effectively restore the fenestrae to a certain degree in LSECs isolated from early to late stages of liver fibrosis mice. Thus, this study highlights the impact of mechanotransduction in LSEC defenestration, and provides novel insights for potential therapeutic interventions for liver fibrosis. |
| Keyword | Liver sinusoidal endothelial cells Fenestrae Liver fibrosis Cytoskeleton remodeling FAK MAPK |
| DOI | 10.1016/j.biomaterials.2023.122462 |
| Indexed By | SCI ; EI |
| Language | 英语 |
| WOS ID | WOS:001165474400001 |
| WOS Keyword | FENESTRAE ; ACTIVATION ; CYTOSKELETON ; FIBROSIS ; SIEVE |
| WOS Research Area | Engineering ; Materials Science |
| WOS Subject | Engineering, Biomedical ; Materials Science, Biomaterials |
| Funding Project | National Natural Science Foundation of China[32130061] ; National Natural Science Foundation of China[T2394512] ; National Natural Science Foundation of China[32271366] ; National Key R & D Program of China[2021YFA0719302] ; China Manned Space Flight Technology Project Chinese Space Station Experiment Project[YYWT0901EXP0701] ; Scientific Instrument Developing Project of Chinese Academy of Sci-ences[GJJSTU20220002] |
| 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 ; Scientific Instrument Developing Project of Chinese Academy of Sci-ences |
| Classification | 一类 |
| Ranking | 1 |
| Contributor | Li, Ning ; Long, Mian |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/94508 |
| Collection | 微重力重点实验室 |
| Affiliation | 1.Chinese Acad Sci, Ctr Biomech & Bioengn, Beijing Key Lab Engn Construct & Mechanobiol, Natl Micrograv Lab,Inst Mech, Beijing 100190, Peoples R China; 2.Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China; 3.Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China; 4.Shandong First Med Univ & Shandong Acad Med Sci, Med Sci & Technol Innovat Ctr, Jinan 250117, Peoples R China; 5.Inst Mech, Chinese Acad Sci, Beijing 100190, Peoples R China |
| Recommended Citation GB/T 7714 | Zhang XY,Li PW,Zhou J,et al. FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration[J]. BIOMATERIALS,2024,305:17.Rp_Au:Li, Ning, Long, Mian |
| APA | 张晓宇.,李培文.,周瑾.,张子良.,吴欢.,...&龙勉.(2024).FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration.BIOMATERIALS,305,17. |
| MLA | 张晓宇,et al."FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration".BIOMATERIALS 305(2024):17. |
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