Related Experiment Video
Updated: Feb 7, 2026
Author Spotlight: Investigating the Pathophysiology of Eosinophilic Esophagitis
Published on: May 10, 2024
Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs
Jie Li1,2, Xiaohu Ren3, Lingwei Wang1
1Department of Respiratory Diseases, Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
Insights
Thermal injury increases lung permeability and edema by damaging intercellular junctions. Heat activates c-Src kinase and reduces p120ctn, leading to junction protein breakdown and dissociation, causing pulmonary edema.
Area of Science:
- Cell biology
- Pulmonary medicine
- Toxicology
Background:
- Thermal injury is a significant cause of pulmonary edema and mortality.
- Intercellular junctions, including adhesive (p120ctn, E-cadherin, α-catenin, β-catenin) and compact (occludin, ZO-1) types, maintain lung epithelial integrity.
- The precise mechanism by which heat disrupts these junctions and induces pulmonary edema is not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying thermal injury-induced pulmonary edema.
- To investigate the role of intercellular junction proteins and c-Src kinase in heat-induced lung injury.
- To evaluate potential therapeutic interventions targeting these pathways.
Main Methods:
- Utilized mouse lung epithelial (MLE-12) cells and a Wistar rat model of thermal inhalation injury.
- Investigated the effects of heat treatment on intercellular junction protein expression and localization using Western blotting, real-time PCR, and co-immunoprecipitation.
- Assessed the impact of c-Src inhibition (PP2) and p120ctn modulation (siRNA, cDNA) on cellular permeability and lung injury.
Main Results:
- Heat exposure increased cell permeability, degraded ZO-1, occludin, α-catenin, and β-catenin, and reduced E-cadherin membrane distribution.
- Heat activated c-Src kinase, decreased p120ctn expression, and disrupted occludin-ZO-1 complex formation.
- Inhibition of c-Src and overexpression of p120ctn ameliorated heat-induced junction disruption and attenuated lung injury in vivo.
Conclusions:
- Heat-induced pulmonary edema results from intercellular junction protein degradation and dissociation.
- The c-Src kinase pathway, activated by heat, and downregulation of p120ctn expression are key mediators of this process.
- Targeting c-Src kinase and modulating p120ctn expression show therapeutic potential for thermal lung injury.
Background/Aims:
Thermal injury causes pulmonary edema and can lead to death. Intercellular junctions are composed of adhesive (p120ctn, E-cadherin, α-catenin and β-catenin) and compact (occludin and ZO-1) junctions. Heat deteriorates intercellular junctions and increases cell gaps to ultimately induce pulmonary edema, but the underlying mechanism remains elusive.
Methods:
Mouse lung epithelial (MLE-12) cells pre-treated with the c-Src inhibitor PP2, p120ctn catenin (p120ctn) small interfering RNA and p120ctn catenin (p120ctn) complementary DNA were subjected to heat treatment. Western blotting and real-time polymerase chain reaction assays were used to evaluate junction protein expression changes after heat treatment, and co-immunoprecipitation was used to test the binding state of junction proteins. In addition, hematoxylin and eosin staining and immunohistochemistry were used to evaluate changes in junction protein expression and lung injury in a Wistar rat model of thermal inhalation injury.
Results:
Heat increased cell permeability; induced ZO-1, occludin, α-catenin and β-catenin degradation; and decreased E-cadherin distribution in cell membranes. Heat also activated c-Src and decreased both p120ctn expression levels and occludin and ZO-1 association. c-Src inhibitor (PP2) treatment and p120ctn overexpression reversed these effects and attenuated lung injury in vivo.
Conclusion:
Heat induces junction protein degradation and dissociation to increase membrane permeability and cause lung edema via c-Src kinase activation and p120ctn expression downregulation.
More Related Videos
Related Concept Videos
02:24Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
02:24Regulation of Expression Occurs at Multiple Steps
02:54Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:23Regulation of Expression at Multiple Steps
01:27Constitutive and Regulated Gene Expression
01:16Specific Heat
For example, increasing the temperature of one gram of water by 1°C requires one calorie of heat energy and can be written as 1 cal/g-°C, or...