New insights into the suppression of inflammation and lipid accumulation by <em>JAZF1</em>

Wujun Chen; Yingjie Zhong; Yang Yuan; Meng Zhu; Wenchao Hu; Ning Liu; Dongming Xing

doi:10.1016/j.gendis.2022.10.029

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New insights into the suppression of inflammation and lipid accumulation by JAZF1

Review Articles | 更新时间：2024-02-04

- New insights into the suppression of inflammation and lipid accumulation by JAZF1
- New insights into the suppression of inflammation and lipid accumulation by JAZF1
- Genes & Diseases 2023年1卷第6期页码：2457-2469
- 作者机构：
  
  1. Cancer Institute, Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute,Shandong,Qingdao,China,266071
  2. Department of Endocrinology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University,Shandong,Qingdao,China,266035
  3. School of Life Sciences, Tsinghua University,Beijing,China,100084
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.10.029
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-11-1，
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New insights into the suppression of inflammation and lipid accumulation by JAZF1[J]. Genes & Diseases, 2023,1(6):2457-2469.

Wujun Chen, Yingjie Zhong, Yang Yuan, et al. New insights into the suppression of inflammation and lipid accumulation by JAZF1[J]. Genes & Diseases, 2023,1(6):2457-2469.
New insights into the suppression of inflammation and lipid accumulation by JAZF1[J]. Genes & Diseases, 2023,1(6):2457-2469. DOI： 10.1016/j.gendis.2022.10.029.

Wujun Chen, Yingjie Zhong, Yang Yuan, et al. New insights into the suppression of inflammation and lipid accumulation by JAZF1[J]. Genes & Diseases, 2023,1(6):2457-2469. DOI： 10.1016/j.gendis.2022.10.029.

摘要

Abstract

herosclerosis is one of the leading causes of disease and death worldwide. The identification of new therapeutic targets and agents is critical.

JAZF1

is expressed in many tissues and is found at particularly high levels in adipose tissue (AT).

JAZF1

suppresses inflammation (including

IL-1β

IL-4

IL-6

IL-8

IL-10

TNFα

IFN-γ

IAR-20

COL3A1

laminin

and

MCP-1

) by reducing

NF-κB

pathway activation and AT immune cell infiltration.

JAZF1

reduces lipid accumulation by regulating the liver X receptor response element (

LXRE

) of the

SREBP-1c

promoter

the

cAMP

-response element (

CRE

) of

HMGCR

and the

TR4

axis.

LXRE

and

CRE

sites are present in many cytokine and lipid metabolism gene promoters

which suggests that

JAZF1

regulates these genes through these sites.

NF-κB

is the center of the

JAZF1

-mediated inhibition of the inflammatory response.

JAZF1

suppresses

NF-κB

expression by suppressing

TAK1

expression. Interestingly

TAK1

inhibition also decreases lipid accumulation. A dual-targeting strategy of

NF-κB

and

TAK1

could inhibit both inflammation and lipid accumulation. Dual-target compounds (including prodrugs) 1–5 exhibit nanomolar inhibition by targeting

NF-κB

and

TAK1

EGFR

COX-2

. However

the

NF-κB

suppressing activity of these compounds is relatively low (IC

300 nM). Compounds 6–14 suppress

NF-κB

expression with IC

values ranging from 1.8 nM to 38.6 nM. HS-276 is a highly selective

orally bioavailable

TAK1

inhibitor. Combined structural modifications of compounds using a prodrug strategy may enhance

NF-κB

inhibition. This review focused on the role and mechanism of

JAZF1

in inflammation and lipid accumulation for the identification of new anti-atherosclerotic targets.

关键词

Keywords

AtherosclerosisCREJAZF1LXRENF-κBTAK1

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New insights into the suppression of inflammation and lipid accumulation by JAZF1

New insights into the suppression of inflammation and lipid accumulation by JAZF1

DOI：10.1016/j.gendis.2022.10.029

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Abstract

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Keywords

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