Compound c17 alleviates inflammatory cardiomyopathy in streptozotocin-induced diabetic mice by targeting MyD88

doi:10.1016/j.intimp.2023.110863

科研成果详情

题名	Compound c17 alleviates inflammatory cardiomyopathy in streptozotocin-induced diabetic mice by targeting MyD88
作者	Zhang, Qianhui1,2; Zhu, Weiwei2,3; Lou, Shuaijie2; Bao, Hongdan1; Zhou, Yafen 1; Cai, Zhaohong1; Ye, Jiaxi2; Cui, Yaqian2; Wang, Minxiu2; Jin, Leiming 2; Liang, Guang2,4; Luo, Wu2,3; Wang, Yi1,2,5
发表日期	2023-11
发表期刊	International immunopharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Diabetic cardiomyopathy Inflammation MyD88 c17
其他关键词	INSULIN-RESISTANCE ; HYPERGLYCEMIA ; INHIBITION ; UPDATE
摘要	Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus and is associated with increased morbidity and mortality due to cardiac dysfunction. Chronic inflammation plays a significant role in the development of DCM, making it a promising target for novel pharmacological strategies. Our previous study has synthesized a novel compound, c17, which exhibited strong anti-inflammatory activity by specifically targeting to myeloid differentiation primary response 88 (MyD88). In this study, we evaluated the therapeutic effect of c17 in DCM., The small molecular selective MyD88 inhibitor, c17, was used to evaluate the effect of MyD88 on DCM in both high concentration of glucose- and palmitic acid-stimulated macrophages and streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) mice., The treatment of c17 in T1DM mice resulted in improved heart function and reduced cardiac hypertrophy, inflammation and fibrogenesis. RNA sequencing analysis of the heart tissues revealed that c17 effectively suppressed the inflammatory response by regulating the MyD88-dependent pathway. Co-immunoprecipitation experiments further confirmed that c17 disrupted the interaction between MyD88 and Toll-like receptor 4 (TLR4), consequently inhibiting downstream NF-κB activation. In vitro studies demonstrated that c17 exhibited similar anti-inflammatory activity by targeting MyD88 in macrophages, which are the primary regulators of cardiac inflammation. Furthermore, conditioned medium derived from c17-treated macrophages showed reduced capacity to induce hypertrophy, pro-fibrotic reactions, and secondary inflammation in cardiomyocytes., In conclusion, the small-molecule MyD88 inhibitor, c17, effectively combated the inflammatory DCM, therefore could be a potential candidate for the treatment of this disease.
资助项目	National Natural Science Founda-tion of China [81970338, 82170373]; Key Research Project of Wenzhou City [ZY2021021]
出版者	ELSEVIER
ISSN	1567-5769
EISSN	1878-1705
卷号	124 期号:Pt A
DOI	10.1016/j.intimp.2023.110863
页数	10
WOS类目	Immunology ; Pharmacology & Pharmacy
WOS研究方向	Immunology ; Pharmacology & Pharmacy
WOS记录号	WOS:001075851200001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-09
URL	查看原文
PubMed ID	37703787
SCOPUSEID	2-s2.0-85170407810
通讯作者地址	[Luo, Wu]Joint Research Centre on Medicine,the Affiliated Xiangshan Hospital of Wenzhou Medical University,Zhejiang,Ningbo,315700,China
Scopus学科分类	Immunology and Allergy;Immunology;Pharmacology
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182880
专题	其他_附属象山医院（象山县第一人民医院）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其他_附属萧山医院（杭州市萧山区第一人民医院）
通讯作者	Luo, Wu
作者单位	1.Joint Research Center on Medicine,the Affiliated Xiangshan Hospital of Wenzhou Medical University,Zhejiang,Ningbo,315700,China; 2.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 3.Medical Research Center,the First Affiliated Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 4.School of Pharmaceutical Sciences,Hangzhou Medical College,Zhejiang,Hangzhou,311399,China; 5.School of Pharmacy,Hangzhou Normal University,Zhejiang,Hangzhou,311399,China
第一作者单位	附属萧山医院（杭州市萧山区第一人民医院）; 附属象山医院（象山县第一人民医院）; 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	附属萧山医院（杭州市萧山区第一人民医院）; 附属象山医院（象山县第一人民医院）
第一作者的第一单位	附属萧山医院（杭州市萧山区第一人民医院）
推荐引用方式 GB/T 7714	Zhang, Qianhui,Zhu, Weiwei,Lou, Shuaijie,et al. Compound c17 alleviates inflammatory cardiomyopathy in streptozotocin-induced diabetic mice by targeting MyD88[J]. International immunopharmacology,2023,124(Pt A).
APA	Zhang, Qianhui., Zhu, Weiwei., Lou, Shuaijie., Bao, Hongdan., Zhou, Yafen., ... & Wang, Yi. (2023). Compound c17 alleviates inflammatory cardiomyopathy in streptozotocin-induced diabetic mice by targeting MyD88. International immunopharmacology, 124(Pt A).
MLA	Zhang, Qianhui,et al."Compound c17 alleviates inflammatory cardiomyopathy in streptozotocin-induced diabetic mice by targeting MyD88".International immunopharmacology 124.Pt A(2023).