Dataset Information

Trim32-DPEP2 axis is an inflammatory switch of macrophages in intestinal inflammation

ABSTRACT: The mechanisms that mediate inflammatory macrophages in intestinal inflammation are incompletely understood. Here, using merged analysis of RNA sequences and mass spectrometry (MS)-based quantitative proteomics, we report the distinction of proteomics and transcriptomics in activated macrophage. Dipeptidase-2 (DPEP2), belonging to DPEP family, is highly expressed and downregulated sharply at protein level but not mRNA level in macrophages responding to inflammatory stimulations. Repression of DPEP2 not only enhances macrophage-mediated intestinal inflammation in vivo but also promotes the production of ROS and the transduction of inflammatory pathways in macrophages in vitro. Mechanistically, DPEP2 inhibits recruitment of inactivated macrophages to inflammatory sites by impairing activation of vimentin (VIM), and DPEP2 downregulation promotes the infiltration of pro-inflammatory macrophages through enhancing the activation of VIM by Akt1. Besides, overexpressed DPEP2 inhibits the transduction of inflammatory signals by resisting MAK3K7 in inactivated macrophages, and DPEP2 is degraded by activated Trim32 resulting in sharp activation of NF-κB and p38 MAPK signals by released MAK3K7 in pro-inflammatory macrophages during the development of intestinal inflammation. Trim32-DPEP2 axis accumulates potential energy of inflammation for macrophages. These results identify DPEP2 as a key regulator of macrophage-mediated intestinal inflammation. Thus, Trim32-DPEP2 axis may be a potential therapeutic target for intestinal inflammation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Macrophage

SUBMITTER: Zhiyan Zhan

LAB HEAD: Zhiyan Zhan

PROVIDER: PXD057405 | Pride | 2025-07-28

REPOSITORIES: Pride

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The Trim32-DPEP2 axis is an inflammatory switch in macrophages during intestinal inflammation.

Zhan Zhiyan Z Liang Huisheng H Zhao Zhuoqi Z Pan Liya L Li Jing J Chen Yuyun Y Xie Zhoulonglong Z Yan Zhilong Z Xiang Ying Y Liu Wenxue W Hong Li L

Cell death and differentiation 20250228 7

The mechanisms via which inflammatory macrophages mediate intestinal inflammation are not completely understood. Herein, using merged analysis of RNA sequencing and mass spectrometry-based quantitative proteomics, we detected differences between proteomic and transcriptomic data in activated macrophages. Dipeptidase-2 (DPEP2), a member of the DPEP family, was highly expressed and then downregulated sharply at the protein level but not at the mRNA level in macrophages in response to inflammatory ...[more]

PMID: 40021897

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