دورية أكاديمية
Siglec-E retards atherosclerosis by inhibiting CD36-mediated foam cell formation
| العنوان: | Siglec-E retards atherosclerosis by inhibiting CD36-mediated foam cell formation |
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| المؤلفون: | Hsu, Yaw Wen, Hsu, Fu Fei, Chiang, Ming Tsai, Tsai, Dong Lin, Li, Fu An, Angata, Takashi, Crocker, Paul R., Chau, Lee Young |
| المصدر: | Hsu , Y W , Hsu , F F , Chiang , M T , Tsai , D L , Li , F A , Angata , T , Crocker , P R & Chau , L Y 2021 , ' Siglec-E retards atherosclerosis by inhibiting CD36-mediated foam cell formation ' , Journal of Biomedical Science , vol. 28 , 5 . https://doi.org/10.1186/s12929-020-00698-zTest |
| سنة النشر: | 2021 |
| المجموعة: | Discovery - University of Dundee Online Publications |
| مصطلحات موضوعية: | Atherosclerosis, CD36, Low-density lipoprotein, Macrophages, Sialic acid, Siglec-E, /dk/atira/pure/subjectarea/asjc/2700/2712, name=Endocrinology, Diabetes and Metabolism, /dk/atira/pure/subjectarea/asjc/1300/1312, name=Molecular Biology, /dk/atira/pure/subjectarea/asjc/1300/1308, name=Clinical Biochemistry, /dk/atira/pure/subjectarea/asjc/1300/1307, name=Cell Biology, /dk/atira/pure/subjectarea/asjc/2700/2704, name=Biochemistry, medical, /dk/atira/pure/subjectarea/asjc/2700/2736, name=Pharmacology (medical) |
| الوصف: | Background : The accumulation of lipid-laden macrophages, foam cells, within sub-endothelial intima is a key feature of early atherosclerosis. Siglec-E, a mouse orthologue of human Siglec-9, is a sialic acid binding lectin predominantly expressed on the surface of myeloid cells to transduce inhibitory signal via recruitment of SH2-domain containing protein tyrosine phosphatase SHP-1/2 upon binding to its sialoglycan ligands. Whether Siglec-E expression on macrophages impacts foam cell formation and atherosclerosis remains to be established. Methods : ApoE-deficient (apoE −/− ) and apoE/Siglec-E-double deficient (apoE −/− /Siglec-E −/− ) mice were placed on high fat diet for 3 months and their lipid profiles and severities of atherosclerosis were assessed. Modified low-density lipoprotein (LDL) uptake and foam cell formation in wild type (WT) and Siglec-E −/− - peritoneal macrophages were examined in vitro. Potential Siglec-E-interacting proteins were identified by proximity labeling in conjunction with proteomic analysis and confirmed by coimmunoprecipitation experiment. Impacts of Siglec-E expression and cell surface sialic acid status on oxidized LDL uptake and signaling involved were examined by biochemical assays. Results : Here we show that genetic deletion of Siglec-E accelerated atherosclerosis without affecting lipid profile in apoE −/− mice. Siglec-E deficiency promotes foam cell formation by enhancing acetylated and oxidized LDL uptake without affecting cholesterol efflux in macrophages in vitro. By performing proximity labeling and proteomic analysis, we identified scavenger receptor CD36 as a cell surface protein interacting with Siglec-E. Further experiments performed in HEK293T cells transiently overexpressing Siglec-E and CD36 and peritoneal macrophages demonstrated that depletion of cell surface sialic acids by treatment with sialyltransferase inhibitor or sialidase did not affect interaction between Siglec-E and CD36 but retarded Siglec-E-mediated inhibition on oxidized LDL uptake. Subsequent ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://discovery.dundee.ac.uk/en/publications/1c85b323-5582-49aa-9165-1b3bfaeeb0f5Test |
| DOI: | 10.1186/s12929-020-00698-z |
| الإتاحة: | https://doi.org/10.1186/s12929-020-00698-zTest https://discovery.dundee.ac.uk/en/publications/1c85b323-5582-49aa-9165-1b3bfaeeb0f5Test https://discovery.dundee.ac.uk/ws/files/55891931/s12929_020_00698_z.pdfTest http://www.scopus.com/inward/record.url?scp=85098645977&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.CF1DD7DA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12929-020-00698-z |
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