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LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells |
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| Authors: | Guozhang He Shuang Kan Shaohua Xu Xuchen Sun Rong Li Wei Shu Ming Chen |
| Institution: | 1. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, China
Collaborative Innovation Center for Guangxi Ethnic Medicine, Guangxi Normal University, Guilin, China Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);2. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, China Collaborative Innovation Center for Guangxi Ethnic Medicine, Guangxi Normal University, Guilin, China Contribution: Data curation (equal), Investigation (equal), Validation (equal);3. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, China Collaborative Innovation Center for Guangxi Ethnic Medicine, Guangxi Normal University, Guilin, China Contribution: Investigation (equal), Methodology (equal), Writing - original draft (equal);4. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, China Collaborative Innovation Center for Guangxi Ethnic Medicine, Guangxi Normal University, Guilin, China Contribution: Data curation (equal), Investigation (equal), Resources (equal);5. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, China Collaborative Innovation Center for Guangxi Ethnic Medicine, Guangxi Normal University, Guilin, China Contribution: Investigation (equal), Resources (equal);6. College of Biotechnology, Guilin Medical University, Guilin, China;7. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, China |
| Abstract: | Endothelial cells (ECs) respond to blood shear stress by changing their morphology is important for maintaining vascular homeostasis. Studies have documented a relationship between endothelial cell shape and the stress flow, and however, the mechanism underlying this cytoskeletal rearrangement due to shear stress remains uncertain. In this paper, we demonstrate that laminar shear stress (LSS) significantly reduces latexin (LXN) expression in ECs. By using siRNA and cell imaging, we demonstrated that LXN knockdown results in the morphologic change and F-actin remodelling just like what LSS does in ECs. We further demonstrate that LXN interacts with Filamin A (FLNA) and regulates FLNA proteolytic cleavage and nuclei translocation. By constructing LXN-/- mice and ApoE-/-LXN-/- double knockout mice, we evaluated the effect of LXN knockout on aortic endothelium damage in mice. We found that LXN deficiency significantly improves vascular permeability, vasodilation and atherosclerosis in mice. Our findings provide confident evidence, for the first time, that LXN is a novel regulator for morphological maintenance of ECs, and LXN deficiency has a protective effect on vascular homeostasis. This provides new strategies and drug targets for the treatment of vascular diseases. |
| Keywords: | atherosclerosis cytoskeleton remodelling endothelial cells laminar shear stress LXN |