GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway
The reduction of pulmonary surfactant (PS) is essential for decreased pulmonary compliance and edema in acute lung injury (ALI). Thyroid transcription factor-1 (TTF-1) plays a major role in the regulation of surfactant protein-A (SP-A), the most abundant protein component of PS. Simultaneously, the...
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| Format: | Article |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/3601454 |
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| author | Tao Zhu Changyi Li Xue Zhang Chunyan Ye Shuo Tang Wei Zhang Jiayang Sun Niwen Huang Fuqiang Wen Daoxin Wang Huojin Deng Jing He Di Qi Wang Deng Tao Yang |
| author_facet | Tao Zhu Changyi Li Xue Zhang Chunyan Ye Shuo Tang Wei Zhang Jiayang Sun Niwen Huang Fuqiang Wen Daoxin Wang Huojin Deng Jing He Di Qi Wang Deng Tao Yang |
| author_sort | Tao Zhu |
| collection | DOAJ |
| description | The reduction of pulmonary surfactant (PS) is essential for decreased pulmonary compliance and edema in acute lung injury (ALI). Thyroid transcription factor-1 (TTF-1) plays a major role in the regulation of surfactant protein-A (SP-A), the most abundant protein component of PS. Simultaneously, the glucagon-like peptide-1 (GLP-1) analogue can enhance SP-A expression in the lung. However, the underlying mechanism is still unknown. The purpose of this study was to explore whether liraglutide, a GLP-1 analogue, upregulates SP-A expression through the TTF-1 signaling pathway in ALI. In vivo, a murine model of ALI was induced by lipopolysaccharide (LPS). Pulmonary inflammation, edema, insulin level, ultrastructural changes in type II alveolar epithelial (ATII) cells, and SP-A and TTF-1 expression were analyzed. In vitro, rat ATII cells were obtained. SP-A and TTF-1 expression in cells was measured. ShRNA-TTF-1 transfection was performed to knock down TTF-1 expression. Our data showed that LPS-induced lung injury and increase in insulin level, and LPS-induced reduction of SP-A and TTF-1 expression in both the lung and cells, were significantly compromised by liraglutide. Furthermore, we also found that these effects of liraglutide were markedly blunted by shRNA-TTF-1. Taken together, our findings suggest that liraglutide enhances SP-A expression in ATII cells and attenuates pulmonary inflammation in LPS-induced ALI, most likely through the TTF-1 signaling pathway. |
| format | Article |
| id | doaj-art-7c79a31c4acb4add8dc0b5bbb7f016ab |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-7c79a31c4acb4add8dc0b5bbb7f016ab2025-08-20T02:07:24ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/36014543601454GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling PathwayTao Zhu0Changyi Li1Xue Zhang2Chunyan Ye3Shuo Tang4Wei Zhang5Jiayang Sun6Niwen Huang7Fuqiang Wen8Daoxin Wang9Huojin Deng10Jing He11Di Qi12Wang Deng13Tao Yang14Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu 610041, ChinaRespiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaLuoyang Orthopedic Hospital of Henan Province, Luoyang 471000, ChinaSchool Hospital of Southern Medical University, Guangzhou 510280, ChinaPain Medicine, Shenzhen Nanshan Hospital, Shenzhen 518052, ChinaRespiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, ChinaRespiratory Medicine, Affiliated Hospital of Guiyang Medical University, Guiyang 550004, ChinaRespiratory Medicine, Affiliated Hospital of Guiyang Medical University, Guiyang 550004, ChinaDivision of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu 610041, ChinaRespiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaRespiratory Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, ChinaRespiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaRespiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaRespiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaThoracic Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaThe reduction of pulmonary surfactant (PS) is essential for decreased pulmonary compliance and edema in acute lung injury (ALI). Thyroid transcription factor-1 (TTF-1) plays a major role in the regulation of surfactant protein-A (SP-A), the most abundant protein component of PS. Simultaneously, the glucagon-like peptide-1 (GLP-1) analogue can enhance SP-A expression in the lung. However, the underlying mechanism is still unknown. The purpose of this study was to explore whether liraglutide, a GLP-1 analogue, upregulates SP-A expression through the TTF-1 signaling pathway in ALI. In vivo, a murine model of ALI was induced by lipopolysaccharide (LPS). Pulmonary inflammation, edema, insulin level, ultrastructural changes in type II alveolar epithelial (ATII) cells, and SP-A and TTF-1 expression were analyzed. In vitro, rat ATII cells were obtained. SP-A and TTF-1 expression in cells was measured. ShRNA-TTF-1 transfection was performed to knock down TTF-1 expression. Our data showed that LPS-induced lung injury and increase in insulin level, and LPS-induced reduction of SP-A and TTF-1 expression in both the lung and cells, were significantly compromised by liraglutide. Furthermore, we also found that these effects of liraglutide were markedly blunted by shRNA-TTF-1. Taken together, our findings suggest that liraglutide enhances SP-A expression in ATII cells and attenuates pulmonary inflammation in LPS-induced ALI, most likely through the TTF-1 signaling pathway.http://dx.doi.org/10.1155/2018/3601454 |
| spellingShingle | Tao Zhu Changyi Li Xue Zhang Chunyan Ye Shuo Tang Wei Zhang Jiayang Sun Niwen Huang Fuqiang Wen Daoxin Wang Huojin Deng Jing He Di Qi Wang Deng Tao Yang GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway Mediators of Inflammation |
| title | GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway |
| title_full | GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway |
| title_fullStr | GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway |
| title_full_unstemmed | GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway |
| title_short | GLP-1 Analogue Liraglutide Enhances SP-A Expression in LPS-Induced Acute Lung Injury through the TTF-1 Signaling Pathway |
| title_sort | glp 1 analogue liraglutide enhances sp a expression in lps induced acute lung injury through the ttf 1 signaling pathway |
| url | http://dx.doi.org/10.1155/2018/3601454 |
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