Related Experiment Video

Updated: Jan 12, 2026

Depletion and Reconstitution of Macrophages in Mice
08:50

Depletion and Reconstitution of Macrophages in Mice

Published on: August 1, 2012

40.4K

Inhibition the MAP3K20-mediated ribotoxic stress response pathway downregulates M1 macrophage polarization in

Wan-Yu Xia1, Xin-Yuan Ma2, Zi-Meng Zhu1

  • 1Acupuncture and Moxibustion School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

International Immunopharmacology
|November 5, 2025
PubMed

Insights

This study reveals how ribotoxic stress response (RSR) drives M1 macrophage polarization in ulcerative colitis (UC). Targeting MAP3K20 kinase with Vemurafenib shows promise for treating UC by reducing inflammation.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Ulcerative colitis (UC) involves complex immune dysregulation.
  • M1 macrophage polarization contributes to UC pathogenesis.
  • Ribotoxic stress response (RSR) role in UC is not fully understood.

Purpose of the Study:

  • Investigate RSR activation of M1 macrophage polarization in UC.
  • Identify key genes and pathways involved in RSR-mediated M1 polarization in UC.
  • Evaluate MAP3K20 as a therapeutic target for UC.

Main Methods:

  • Gene Set Variation Analysis (GSVA) of intestinal tissues.
  • Weighted gene co-expression network analysis (WGCNA) for RSR hub genes.
  • Single-cell RNA sequencing.
  • Dextran Sodium Sulfate (DSS)-induced UC models.

Main Results:

  • Identified six core RSR hub genes (SNAL1, MDM2, MAPK11, MAP3K20, E2F1, BMP6).
  • Established MAP3K20 as the pivotal kinase in RSR-mediated M1 macrophage polarization in UC.
  • MAP3K20 regulates JNK/p38 signaling, driving M1 polarization and UC inflammation.
  • Vemurafenib (MAP3K20 inhibitor) attenuated inflammation and pathological damage in UC models.

Conclusions:

  • MAP3K20 is a key mediator of RSR-driven M1 macrophage polarization in UC.
  • Targeting MAP3K20 offers a potential therapeutic strategy for ulcerative colitis.
  • This research provides novel insights into UC pathogenesis and treatment.
Keywords:
M1 macrophagesMAP3K20Ribotoxic stress responseUlcerative colitis

More Related Videos

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

7.6K
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages10:07

Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages

Published on: June 23, 2013

68.2K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
Inflammatory Bowel Disease I: Ulcerative Colitis01:27

Inflammatory Bowel Disease I: Ulcerative Colitis

Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
882