論文 - 詳細
| RRC ID | 81916 |
|---|---|
| 著者 | He G, Kan S, Xu S, Sun X, Li R, Shu W, Chen M. |
| タイトル | LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells. |
| ジャーナル | J Cell Mol Med |
| 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. |
| 巻・号 | 25(14) |
| ページ | 6815-6827 |
| 公開日 | 2021-7-1 |
| DOI | 10.1111/jcmm.16685 |
| PMID | 34085389 |
| PMC | PMC8278077 |
| MeSH | Animals Aorta / cytology Aorta / metabolism Aorta / physiology Apolipoproteins E / genetics Blood Circulation Cytoskeleton / metabolism* Endothelium, Vascular / cytology Endothelium, Vascular / metabolism* Endothelium, Vascular / physiology Filamins / metabolism* Human Umbilical Vein Endothelial Cells / metabolism Humans Mice Mice, Inbred C57BL Nerve Tissue Proteins / deficiency Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Proteolysis Stress, Mechanical Vasodilation |
| IF | 4.486 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC03456 |