FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration

doi:10.1016/j.biomaterials.2023.122462

	FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration
	Zhang, Xiaoyu 3,4,5; Li, Peiwen 4,5; Zhou, Jin 4,5; Zhang, Ziliang 2,4,5; Wu, Huan 4,5; Shu, Xinyu 3,4,5; Li, Wang 3,4,5; Wu, Yi 3,4,5; Du, Yu 4,5; Lu, Dongyuan 3,4,5
刊名	BIOMATERIALS
	2024-03-01
卷号	305 页码:17
关键词	Liver sinusoidal endothelial cells Fenestrae Liver fibrosis Cytoskeleton remodeling FAK MAPK
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2023.122462
通讯作者	Li, Ning(lining_1@imech.ac.cn) ; Long, Mian(mlong@imech.ac.cn)
英文摘要	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.
资助项目	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]
WOS关键词	FENESTRAE ; ACTIVATION ; CYTOSKELETON ; FIBROSIS ; SIEVE
WOS研究方向	Engineering ; Materials Science
语种	英语
WOS记录号	WOS:001165474400001
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 ; Scientific Instrument Developing Project of Chinese Academy of Sci-ences
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/94507]
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.Inst Mech, Chinese Acad Sci, Beijing 100190, Peoples R China 2.Shandong First Med Univ & Shandong Acad Med Sci, Med Sci & Technol Innovat Ctr, Jinan 250117, Peoples R China 3.Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Natl Micrograv Lab, Beijing 100190, Peoples R China 5.Chinese Acad Sci, Ctr Biomech & Bioengn, Beijing Key Lab Engn Construct & Mechanobiol, Natl Micrograv Lab,Inst Mech, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Xiaoyu,Li, Peiwen,Zhou, Jin,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.
APA	Zhang, Xiaoyu.,Li, Peiwen.,Zhou, Jin.,Zhang, Ziliang.,Wu, Huan.,...&Long, Mian.(2024).FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration.BIOMATERIALS,305,17.
MLA	Zhang, Xiaoyu,et al."FAK-p38 signaling serves as a potential target for reverting matrix stiffness-modulated liver sinusoidal endothelial cell defenestration".BIOMATERIALS 305(2024):17.