Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase2: A new therapy target in glycocalyx shedding

doi:10.1111/bph.16288

IOCAS-IR > 实验海洋生物学重点实验室

	Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase2: A new therapy target in glycocalyx shedding
	Li, Zhi1,2,3,4 ; Wu, Ning 1,4,5,6; Wang, Jing1,3 ; Yue, Yang1,3 ; Geng, Lihua 1,3; Zhang, Quanbin 1,3,4,6
	2024-01-23
发表期刊	BRITISH JOURNAL OF PHARMACOLOGY
ISSN	0007-1188
页码	17
通讯作者	Wu, Ning(wuning@qdio.ac.cn) ; Zhang, Quanbin(qbzhang@qdio.ac.cn)
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.
关键词	diabetic vascular complication glycocalyx insulin resistance LMWF NEU2
DOI	10.1111/bph.16288
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Pharmacology & Pharmacy
WOS记录号	WOS:001147387800001
出版者	WILEY
WOS关键词	CONCISE GUIDE ; PERMEABILITY ; DYSFUNCTION ; EXPRESSION ; SULFATE
引用统计
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/184267
专题	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.Chinese Acad Sci, Inst Oceanol, Ctr Ocean Megasci, CAS & Shandong Prov Key Lab Expt Marine Biol, Qingdao 266071, 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.Natl Lab Marine Sci & Technol Qingdao, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China 4.Natl Lab Marine Sci & Technol Qingdao, Lab Marine Drugs & Biol Prod, Qingdao, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Chinese Acad Sci, Inst Oceanol, Marine Bioact Subst, 7 Nanhai Rd, Qingdao 266071, Peoples R China
第一作者单位	中国科学院海洋大科学研究中心
通讯作者单位	中国科学院海洋大科学研究中心; 中国科学院海洋研究所
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.