Open Access

ARTICLE

Lysine demethylase 5B transcriptionally regulates TREM1 in human cardiac fibroblasts

by CHUNLING LIANG^1,#, JING CHEN^2,#, XIAOJIE CHEN¹, WEI YAN³, JIE YU^4,*

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

* Corresponding Author: JIE YU. Email:

BIOCELL 2024, 48(7), 1105-1113. https://doi.org/10.32604/biocell.2024.050509

Received 08 February 2024; Accepted 10 April 2024; Issue published 03 July 2024

Abstract

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. Myocardial fibrosis following myocardial infarction significantly contributes to cardiac dysfunction. Objectives: This study aimed to unveil the intrinsic regulatory mechanism of TREM1 in myocardial fibrosis. Methods: Mimicking pathology by angiotensin II (Ang II) treatment of human cardiac fibroblasts (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 myocardial fibrosis. This finding provides a theoretical foundation for understanding disease pathology and potentially advancing the development of new targeted therapies.

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