Related Experiment Video

Updated: Sep 20, 2025

Rapid Depletion of Renal Macrophages using Human CD59/Intermedilysin Cell Ablation Tool
10:15

Rapid Depletion of Renal Macrophages using Human CD59/Intermedilysin Cell Ablation Tool

Published on: May 9, 2025

343

Inhibition of IRE1α Alleviates Renal Fibrosis and Downregulates M1 Macrophage Activation via the p38 MAPK Pathway

Zichan Guo1,2, Yuting Shen2,3, Xiaxia Yu2

  • 1Faculty of Life Sciences, Northwest University, Xi'an, China.

Immunology
|May 23, 2025
PubMed

Insights

Endoplasmic reticulum (ER) stress drives M1 macrophage activation, worsening kidney fibrosis in a mouse model. Inhibiting ER stress or specific pathways like IRE1α shows promise for treating renal fibrosis.

Area of Science:

  • Nephrology
  • Immunology
  • Cellular Biology

Background:

  • M1 macrophage activation and endoplasmic reticulum (ER) stress are implicated in renal fibrosis progression.
  • The precise mechanisms linking ER stress to M1 macrophage activation in kidney fibrosis require elucidation.

Purpose of the Study:

  • To investigate the role of ER stress in M1 macrophage activation within the unilateral ureteral obstruction (UUO) mouse model.
  • To elucidate the underlying molecular mechanisms connecting ER stress to M1 macrophage activation and renal fibrosis.

Main Methods:

  • Utilized the UUO mouse model to study renal fibrosis.
  • Administered ER stress inhibitors (4-PBA) and IRE1α inhibitors (4μ8C).
  • Examined M1 macrophage activation, ER stress markers, and the IRE1α/XBP1s-p38 MAPK pathway.

Main Results:

  • UUO induced significant M1 macrophage activation and ER stress in early renal fibrosis.
  • ER stress inhibition (4-PBA) suppressed M1 macrophage activation and alleviated renal fibrosis.
  • IRE1α inhibition (4μ8C) reduced ER stress, M1 macrophage activation, and improved renal fibrosis.
  • ER stress-mediated M1 macrophage activation was found to be regulated by the IRE1α/XBP1s-p38 MAPK pathway.

Conclusions:

  • ER stress significantly contributes to M1 macrophage activation in the UUO model of renal fibrosis.
  • Targeting the ER stress pathway, particularly the IRE1α/XBP1s-p38 MAPK axis, offers a novel therapeutic strategy for renal fibrosis.
Keywords:
IRE1αM1 macrophageendoplasmic reticulum stressp38 MAPKrenal fibrosis

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