Faculty Collaboration Database

Inflammatory metabolite 7α,25-OHC promotes TIMP1 expression in COVID-19 monocytes through synergy effect of SMARCC1/JUND/H3K27ac. Cell Mol Life Sci 2025 May 21;82(1):208

Date

05/22/2025

Pubmed ID

40399563

Pubmed Central ID

PMC12095718

DOI

10.1007/s00018-025-05721-w

Scopus ID

2-s2.0-105005585248 (requires institutional sign-in at Scopus site)

Abstract

Chromatin remodeling factors are involved in the inflammatory responses, contributing to tissue damage and multi-organ dysfunction in COVID-19 patients. However, the underlying mechanisms remain unclear. In this study, high-dimensional analyses of single-cell RNA sequencing and single-cell ATAC sequencing data revealed increased chromatin accessibility at the promoters or enhancers of the pro-inflammatory cytokine tissue inhibitor of metalloproteinase-1 (TIMP1), as well as altered gene transcription profiles in monocytes from COVID-19 patients. Motif enrichment and positive regulators analyses identified SMARCC1, the core subunit of the chromatin remodeling complex, and the transcription factor JUND as positive regulators to co-modulate TIMP1 expression. In-vitro experiments, co-immunoprecipitation and chromatin immunoprecipitation (ChIP)-qPCR, and others, demonstrated the collaboration of SMARCC1 and JUND. Increased 7α,25-dihydroxycholesterol (7α,25-OHC) enhanced SMARCC1-JUND interactions to co-regulate TIMP1 expression. Further investigation indicated that 7α,25-OHC promoted the expression of SMARCC1 and its co-localization with H3K27ac, which involved in the expression of TIMP1 and inflammatory responses. Our study highlights the critical roles of SMARCC1 and JUND in COVID-19 inflammation, and offers the potential targets for the prevention and treatment of COVID-19.

Author List

Feng Y, Wu Z, Hu K, Yuan S, Li J, Wang Y, Wang Z, Yang H, Luo ZH, Zhou J

Author

Jake Luo Ph.D. Associate Professor; Director, Center for Biomedical Data and Language Processing (BioDLP) in the Health Informatics & Administration department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Gene Expression Regulation
Histones
Humans
Inflammation
Monocytes
Tissue Inhibitor of Metalloproteinase-1
Transcription Factors