2. Academic Validation
  3. BRD2 promotes inflammation and lipid accumulation through the NF-κB pathway in alcoholic liver injury

BRD2 promotes inflammation and lipid accumulation through the NF-κB pathway in alcoholic liver injury

  • Biochem Pharmacol. 2025 Oct 19;243(Pt 1):117442. doi: 10.1016/j.bcp.2025.117442.
Juanjuan Li 1,  Haidi Li 2,  Miao Cheng 2,  Zhifan Chen 3,  Li Sun 3,  Cheng Huang 4,  Yin Xu 5,  Jun Li 6
Affiliations

Affiliations

  • 1 School of Mental Health and Psychological Sciences, Laboratory of Molecular Neuropsychiatry, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, China.
  • 2 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China.
  • 3 School of Mental Health and Psychological Sciences, Laboratory of Molecular Neuropsychiatry, Anhui Medical University, Hefei 230032, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, China.
  • 4 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China. Electronic address: huangcheng@ahmu.edu.cn.
  • 5 School of Mental Health and Psychological Sciences, Laboratory of Molecular Neuropsychiatry, Anhui Medical University, Hefei 230032, China; Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, China. Electronic address: xuyin@ahmu.edu.cn.
  • 6 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmaceutical Sciences, Anhui Medical University, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
PMID: 41120012 DOI: 10.1016/j.bcp.2025.117442
Abstract

Alcoholic liver injury (ALI) is a significant global health burden, characterized by hepatic inflammation and metabolic dysfunction. This study revealed a critical role of Bromodomain-containing Protein 2 (BRD2) in regulating macrophage-mediated inflammation during ALI. We demonstrated that BRD2 expression is significantly upregulated in both the liver tissue and primary Kupffer cells following ALI. Adenovirus -mediated BRD2 knockdown markedly attenuated inflammatory responses and, reduced lipid accumulation and liver injury in EtOH-fed mice. Mechanistically, BRD2 modulates macrophage activation through the Nuclear Factor Kappa B (NF-κB) signaling pathway, as evidenced by altered P65 phosphorylation following BRD2 manipulation. Furthermore, we identified a paracrine interaction between BRD2-activated macrophages and hepatocytes, wherein inflammatory mediators from BRD2-overexpressing macrophages promoted lipid accumulation in hepatocytes. These findings highlight that BRD2 as a key epigenetic regulator of inflammation and lipid metabolism in ALI, offering a promising therapeutic target for addressing both inflammatory and metabolic components of the disease.

Keywords

Alcoholic liver injury; BRD2; Inflammation; Lipid metabolism; Macrophage; NF-κB pathway.

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