Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs
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 ind...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-07-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/491723 |
| _version_ | 1819091677310091264 |
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| author | Jie Li Xiaohu Ren Lingwei Wang Xiu Yu Khalid Khan Mengjie Feng Qi He Huanmin Luo Chen Qiu |
| author_facet | Jie Li Xiaohu Ren Lingwei Wang Xiu Yu Khalid Khan Mengjie Feng Qi He Huanmin Luo Chen Qiu |
| author_sort | Jie Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T22:43:31Z |
| format | Article |
| id | doaj.art-a59dc3788e4547d79cd1abac2b764ccc |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-21T22:43:31Z |
| publishDate | 2018-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-a59dc3788e4547d79cd1abac2b764ccc2022-12-21T18:47:47ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-07-0148123725010.1159/000491723491723Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the LungsJie LiXiaohu RenLingwei WangXiu YuKhalid KhanMengjie FengQi HeHuanmin LuoChen QiuBackground/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.https://www.karger.com/Article/FullText/491723HeatThermal inhalation injuryP120ctnC-SrcCell junction |
| spellingShingle | Jie Li Xiaohu Ren Lingwei Wang Xiu Yu Khalid Khan Mengjie Feng Qi He Huanmin Luo Chen Qiu Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs Cellular Physiology and Biochemistry Heat Thermal inhalation injury P120ctn C-Src Cell junction |
| title | Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs |
| title_full | Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs |
| title_fullStr | Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs |
| title_full_unstemmed | Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs |
| title_short | Heat-Induced Epithelial Barrier Dysfunction Occurs via C-Src Kinase and P120ctn Expression Regulation in the Lungs |
| title_sort | heat induced epithelial barrier dysfunction occurs via c src kinase and p120ctn expression regulation in the lungs |
| topic | Heat Thermal inhalation injury P120ctn C-Src Cell junction |
| url | https://www.karger.com/Article/FullText/491723 |
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