Blockage of MyD88 in cardiomyocytes alleviates cardiac inflammation and cardiomyopathy in experimental diabetic mice.

doi:10.1016/j.bcp.2022.115292

科研成果详情

题名	Blockage of MyD88 in cardiomyocytes alleviates cardiac inflammation and cardiomyopathy in experimental diabetic mice.
作者	Luo, Wu1,2; Wu, Gaojun1; Chen, Xiaojun 2; Zhang, Qiuyan 2; Zou, Chunpeng3; Wang, Jun 5; Liu, Jun1; Chattipakorn, Nipon 6; Wang, Yi2; Liang, Guang1,2,4
发表日期	2022-12
发表期刊	Biochemical pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article ; Research Support, Non-U.S. Gov't
关键词	Cardiomyocytes Diabetic cardiomyopathy Fibrosis Inflammation MyD88
其他关键词	EXPRESSION ; MECHANISMS ; APOPTOSIS ; PROTECTS ; FIBROSIS ; DISEASE ; MODEL
摘要	Hyperglycemia-associated inflammation contributes to diabetic cardiomyopathy. Myeloid differentiation primary-response protein 88 (MyD88) is an adapter protein of many Toll-like receptors (TLRs) and is recruited to TLRs to initiate inflammatory response in endotoxin-activated innate immunity. However, the role of MyD88 in diabetic cardiomyopathy is unknown. We examined the role and mechanism of MyD88 in inflammatory heart injuries in diabetes and identified MyD88 as a potential target for the treatment of diabetic cardiomyopathy. In this study, we first found that MyD88 expression was increased in cardiomyocytes of diabetic mouse hearts. In cultured cardiomyocytes, MyD88 inhibition either by siRNA or by small-molecular inhibitor LM8 markedly blocked TLR4-MyD88 complex formation, reduced pro-inflammatory mitogen-activated protein kinases/nuclear factor-κB (MAPKs/NF-κB) cascade activation and decreased pro-inflammatory cytokine expression under high glucose condition. Moreover, pharmacologic inhibition of MyD88 by LM8 showed significantly anti-inflammatory, anti-hypertrophic and anti-fibrotic effects in the hearts of both type 1 and type 2 diabetic mice. These beneficial effects of MyD88 inhibition were correlated to the reduced activation of TLR4-MyD88-MAPKs/NF-κB signaling pathways in the hearts. Taken together, MyD88 in cardiomyocytes mediates diabetes-induced cardiac inflammatory injuries and pharmacological inhibition of MyD88 shows significantly cardioprotective effects, indicating MyD88 as a potential therapeutic target for diabetic cardiomyopathy.
资助项目	National Key Research Project [2017YFA0506000]; National Natural Science Foundation of China [82000793, 21961142009]; Thailand Research Found Grant [DBG6280006]; Natural Science Foundation of Zhejiang Province [LY18H020013, LY19H020004]; Zhejiang Provincial Key Scientific Project [2021C03041]; Wenzhou Science and Technology Key Project [2018ZY009]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
ISSN	0006-2952
EISSN	1873-2968
卷号	206 页码:115292
DOI	10.1016/j.bcp.2022.115292
页数	14
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000878683000007
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	36241098
SCOPUSEID	2-s2.0-85140354555
通讯作者地址	[Liang, Guang]Department of Cardiology and Medical Research Center,the First Affiliated Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Biochemistry;Pharmacology
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/166911
专题	附属第一医院附属第二医院第二临床医学院、附属第二医院、育英儿童医院药学院（分析测试中心）_生物有机与药物化学研究中心第二临床医学院、附属第二医院、育英儿童医院_影像医学与核医学_超声科
通讯作者	Liang, Guang
作者单位	1.Department of Cardiology and Medical Research Center,the First Affiliated Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 3.Department of Ultrasonography,the Second Affiliated Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 4.School of Pharmaceutical Sciences,Hangzhou Medical College,Zhejiang,Hangzhou,311399,China; 5.Department of Cardiology,Wenzhou Central Hospital,Zhejiang,Wenzhou,325035,China; 6.Cardiac Electrophysiology Research and Training Center,Faculty of Medicine,Chiang Mai University,Chiang Mai,50200,Thailand
第一作者单位	附属第一医院; 药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Luo, Wu,Wu, Gaojun,Chen, Xiaojun,et al. Blockage of MyD88 in cardiomyocytes alleviates cardiac inflammation and cardiomyopathy in experimental diabetic mice.[J]. Biochemical pharmacology,2022,206:115292.
APA	Luo, Wu., Wu, Gaojun., Chen, Xiaojun., Zhang, Qiuyan., Zou, Chunpeng., ... & Liang, Guang. (2022). Blockage of MyD88 in cardiomyocytes alleviates cardiac inflammation and cardiomyopathy in experimental diabetic mice.. Biochemical pharmacology, 206, 115292.
MLA	Luo, Wu,et al."Blockage of MyD88 in cardiomyocytes alleviates cardiac inflammation and cardiomyopathy in experimental diabetic mice.".Biochemical pharmacology 206(2022):115292.