LINC00461 promotes macrophage M1 polarization by inhibiting KLF4 transcription

LINC00461 promotes macrophage M1 polarization by inhibiting KLF4 transcription

Background: Macrophage polarization is a complex process whereby macrophages differentiate into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes, mediating distinct and often opposing functions in immunity and tissue repair. Methods: We analyzed LINC00461 expression in M1- and M2-polarized...

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Bibliographic Details
Main Authors: Bicong Gao, Kaitong Jia, You Ya, Rui Tian, Xiaochen Wang, Zheng Huang, Feng Gao
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Immunobiology
Subjects:
LINC00461
Macrophage polarization
KLF4
DNA methyltransferases
Online Access:http://www.sciencedirect.com/science/article/pii/S0171298525002384
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Summary:Background: Macrophage polarization is a complex process whereby macrophages differentiate into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes, mediating distinct and often opposing functions in immunity and tissue repair. Methods: We analyzed LINC00461 expression in M1- and M2-polarized macrophages using qPCR. Functional assays (in vitro and in vivo) were performed to assess the effects of LINC00461 knockdown on cytokine secretion. RNA-seq, bisulfite sequencing, and chromatin immunoprecipitation (ChIP) were used to explore the mechanism involving Kruppel-like factor 4 (KLF4) and DNA methylation. Results: LINC00461 levels were elevated in M1 macrophages and reduced in M2 macrophages. Knockdown of LINC00461 attenuated pro-inflammatory cytokine release (e.g., IL-1β, TNF-α) in M1 cells and promoted anti-inflammatory cytokine secretion (e.g., IL-10, TGF-β) in M2 cells. Mechanistically, LINC00461 knockdown upregulated KLF4 transcription, a key M2 polarization regulator. LINC00461 recruited DNA methyltransferases to induce hypermethylation of the KLF4 promoter, suppressing KLF4 expression and driving M1 polarization. Conclusion: Our findings establish a functional link between LINC00461, KLF4 methylation, and macrophage polarization, providing insights into the epigenetic regulation of inflammatory responses.
ISSN:0171-2985

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