Related Experiment Video
Updated: Jul 12, 2026
09:23
Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples
Published on: May 21, 2021
USP4 controls neutrophil spreading through stabilising IQGAP1 during lung inflammation
Ling Meng1,2, Qinke He1, Shijun Chen3
1Department of Respiratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, People's Republic of China.
Thorax
|July 9, 2026
Summary
Targeting ubiquitin-specific peptidase 4 (USP4) with Vialinin A reduces neutrophil infiltration and lung injury in acute respiratory distress syndrome (ARDS). This USP4-IQGAP1 pathway modulation offers a promising therapeutic strategy for ARDS patients.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Protein homeostasis is crucial for innate immunity and inflammation-mediated tissue damage.
- Modulating protein homeostasis networks in neutrophils may mitigate acute inflammation outcomes.
Purpose of the Study:
- To investigate the role of ubiquitin-specific peptidase 4 (USP4) in neutrophil function during acute lung injury (ALI).
- To elucidate the molecular mechanism of USP4 in neutrophil migration and spreading.
- To evaluate the therapeutic potential of USP4 inhibitors in acute respiratory distress syndrome (ARDS).
Main Methods:
- Established an ALI model in USP4 knockout chimeric mice.
- Utilized CyTOF mass cytometry, quantitative proteomics, and immunoprecipitation-mass spectrometry.
- Performed neutrophil functional assays and assessed therapeutic efficacy of USP4 inhibitor Vialinin A.
Main Results:
- USP4 expression was elevated in ARDS patients and ALI mice.
- USP4 knockout mice showed reduced lung injury and neutrophil infiltration.
- USP4 deubiquitinated IQGAP1, enhancing CDC42 activity and F-actin formation, crucial for neutrophil spreading.
- Vialinin A treatment decreased neutrophil infiltration, improved lung function, and survival in ALI mice.
Conclusions:
- USP4 connects protein homeostasis to neutrophil recruitment in inflammation.
- Targeting the USP4-IQGAP1 pathway with Vialinin A is a potential therapeutic strategy for ARDS.
