Lysine demethylase 5B transcriptionally regulates TREM1 in human cardiac fibroblasts  

作　　者：CHUNLING LIANG JING CHEN XIAOJIE CHEN WEI YAN JIE YU 

机构地区：[1]Department of Emergency,Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing,100102,China [2]Department of Cardiology,State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100102,China [3]Department of Radiology,Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing,100102,China [4]Department of Cardiology,Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing,100102,China

出　　处：《BIOCELL》2024年第7期1105-1113,共9页生物细胞（英文）

摘　　要：Background:A differential gene,triggering receptor expressed on myeloid cells 1(TREM1),was identified in blood sequencing datasets from myocardial infarction patients and healthy controls.Myocardialfibrosis following myocardial infarction significantly contributes to cardiac dysfunction.Objectives:This study aimed to unveil the intrinsic regulatory mechanism of TREM1 in myocardialfibrosis.Methods:Mimicking pathology by angiotensin II(Ang II)treatment of human cardiacfibroblasts(HCFs),the impacts of TREM1 knockdown on its proliferation,migration,and secretion of the pro-fibrotic matrix were identified.Using the Human Transcription Factor Database(HumanTFDB)website,lysine-specific demethylase 5B(KDM5B)was found to bind to the TREM1 promoter,which was further validated through luciferase reporter and chromatin immunoprecipitation(ChIP).By promoting KDM5B overexpression,its effect on the regulation of TREM1 was examined.Results:TREM1 knockdown suppressed the proliferation,migration,and secretion of the pro-fibrotic matrix in HCFs upon Ang II treatment.KDM5B bound to the TREM1 promoter and upregulated its transcriptional expression.Furthermore,KDM5B overexpression reversed the regulation of the above cellular phenotypes by TREM1 knockdown.Conclusion:This study sheds light on the positive regulation of TREM1 by KDM5B,demonstrating their role in promoting myocardialfibrosis.Thisfinding provides a theoretical foundation for understanding disease pathology and potentially advancing the development of new targeted therapies.

关 键 词：Cardiac fibroblasts FIBROSIS Myeloid cell receptor MIGRATION PROLIFERATION 

分 类 号：R541[医药卫生—心血管疾病]