Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase2: A new therapy target in glycocalyx shedding
文献类型:期刊论文
作者 | Li, Zhi2,4,5,6; Wu, Ning1,3,4,5; Wang, Jing4,6; Yue, Yang4,6; Geng, Lihua4,6; Zhang, Quanbin3,4,5,6 |
刊名 | BRITISH JOURNAL OF PHARMACOLOGY |
出版日期 | 2024-01-23 |
页码 | 17 |
ISSN号 | 0007-1188 |
关键词 | diabetic vascular complication glycocalyx insulin resistance LMWF NEU2 |
DOI | 10.1111/bph.16288 |
通讯作者 | Wu, Ning(wuning@qdio.ac.cn) ; Zhang, Quanbin(qbzhang@qdio.ac.cn) |
英文摘要 | Background and PurposeDiabetic vascular complication is a leading cause of disability and mortality in diabetes patients. Low molecular weight fucoidan (LMWF) is a promising drug candidate for vascular complications. Glycocalyx injury predates the occurrence of diabetes vascular complications. Protecting glycocalyx from degradation relieves diabetic vascular complications. LMWF has the potential to protect the diabetes endothelial glycocalyx from shedding.Experimental ApproachThe protective effect of LMWF on diabetic glycocalyx damage was investigated in db/db mice and Human Umbilical Vein Endothelial Cells (HUVEC) through transmission electron microscopy and WGA labelling. The effect of LMWF on glycocalyx degrading enzymes expression was investigated. Neuraminidase2 (NEU2) overexpression/knockdown was performed in HUVECs to verify the important role of NEU2 in glycocalyx homeostasis. The interaction between NEU2 and LMWF was detected by ELISA and surface plasmon resonance analysis (SPR).Key ResultsLMWF normalizes blood indexes including insulin, triglyceride, uric acid and reduces diabetes complications adverse events. LMWF alleviates diabetic endothelial glycocalyx damage in db/db mice kidney/aorta and high concentration glucose treated HUVECs. NEU2 is up-regulated in db/db mice and HUVECs with high concentration glucose. Overexpression/knockdown NEU2 results in glycocalyx shedding in HUVEC. Down-regulation and interaction of LMWF with NEU2 is a new therapy target in glycocalyx homeostasis. NEU2 was positively correlated with phosphorylated IR-beta.Conclusion and ImplicationsNEU2 is an effective target for glycocalyx homeostasis and LMWF is a promising drug to alleviate vascular complications in diabetes by protecting endothelial glycocalyx. |
WOS关键词 | CONCISE GUIDE ; PERMEABILITY ; DYSFUNCTION ; EXPRESSION ; SULFATE |
资助项目 | National Natural Science Foundation of China |
WOS研究方向 | Pharmacology & Pharmacy |
语种 | 英语 |
出版者 | WILEY |
WOS记录号 | WOS:001147387800001 |
源URL | [http://ir.qdio.ac.cn/handle/337002/184266] |
专题 | 海洋研究所_实验海洋生物学重点实验室 |
通讯作者 | Wu, Ning; Zhang, Quanbin |
作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Univ Hlth & Rehabil Sci, Qingdao Municipal Hosp, Qingdao Hosp, Res Ctr Cardiopulm Rehabil,Sch Hlth & Life Sci, Qingdao, Peoples R China 3.Chinese Acad Sci, Inst Oceanol, Marine Bioact Subst, 7 Nanhai Rd, Qingdao 266071, Peoples R China 4.Chinese Acad Sci, Inst Oceanol, Ctr Ocean Megasci, CAS & Shandong Prov Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 5.Natl Lab Marine Sci & Technol Qingdao, Lab Marine Drugs & Biol Prod, Qingdao, Peoples R China 6.Natl Lab Marine Sci & Technol Qingdao, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China |
推荐引用方式 GB/T 7714 | Li, Zhi,Wu, Ning,Wang, Jing,et al. Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase2: A new therapy target in glycocalyx shedding[J]. BRITISH JOURNAL OF PHARMACOLOGY,2024:17. |
APA | Li, Zhi,Wu, Ning,Wang, Jing,Yue, Yang,Geng, Lihua,&Zhang, Quanbin.(2024).Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase2: A new therapy target in glycocalyx shedding.BRITISH JOURNAL OF PHARMACOLOGY,17. |
MLA | Li, Zhi,et al."Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase2: A new therapy target in glycocalyx shedding".BRITISH JOURNAL OF PHARMACOLOGY (2024):17. |
入库方式: OAI收割
来源:海洋研究所
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