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MAPK13 controls structural remodeling and disease after epithelial injury
Kangyun Wu1, Yong Zhang1, Dailing Mao1
1Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Biorxiv : the Preprint Server for Biology
|June 19, 2024
Summary
Mitogen-activated protein kinase 13 (MAPK13) controls structural remodeling after epithelial injury. Inhibiting MAPK13 in mice and human cells prevents disease progression, offering a new therapeutic target.
Area of Science:
- Cellular biology
- Molecular medicine
- Respiratory disease research
Background:
- Epithelial repair after injury can lead to structural remodeling and chronic disease.
- Understanding the molecular control of this divergence is crucial for disease modification.
- Stress kinases regulating epithelial stem cells are a potential target for intervention.
Purpose of the Study:
- To investigate the role of mitogen-activated protein kinase 13 (MAPK13) in regulating epithelial stem cells.
- To determine if MAPK13 controls structural remodeling and disease following respiratory viral injury.
- To explore MAPK13 as a potential therapeutic target for remodeling-associated lung diseases.
Main Methods:
- Utilized gene-knockout mouse models of respiratory viral injury.
- Examined MAPK13 regulation in basal-epithelial stem cells (basal-ESCs) using cell culture and organoid formation.
- Analyzed human clinical samples from asthma and COPD patients.
- Performed gene-knockdown experiments in human basal-ESCs.
Main Results:
- Mapk13-knockout mice were protected from structural remodeling, including basal-ESC hyperplasia-metaplasia, immune activation, and mucinous differentiation after injury.
- Mapk13 deficiency attenuated basal-ESC growth and organoid formation in cell models.
- Human basal cells showed increased MAPK13 activity in asthma and COPD samples.
- MAPK13 knockdown inhibited human basal-ESC growth in culture.
Conclusions:
- MAPK13 acts as a key regulator of structural remodeling and disease development after epithelial injury.
- Targeting MAPK13 for down-regulation presents a viable disease-modifying strategy for conditions like asthma and COPD.
Keywords:
asthmachronic obstructive pulmonary disease (COPD)epithelial stem cellmitogen-activated protein kinase (MAPK)p38 kinaserespiratory viral infectionMore Related Videos
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