Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway
Abstract Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of...
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| Format: | Article |
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Nature Portfolio
2021-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-91008-6 |
| _version_ | 1818570492999630848 |
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| author | Shujun Yang Yaodong Song Qiaofang Wang Yanna Liu Zhongwei Wu Xiaojia Duan Yan Zhang Xiuqian Bi Yuanzhang Geng Sanyang Chen Changju Zhu |
| author_facet | Shujun Yang Yaodong Song Qiaofang Wang Yanna Liu Zhongwei Wu Xiaojia Duan Yan Zhang Xiuqian Bi Yuanzhang Geng Sanyang Chen Changju Zhu |
| author_sort | Shujun Yang |
| collection | DOAJ |
| description | Abstract Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of l-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)–signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2–STAT3 signalling. |
| first_indexed | 2024-12-14T13:42:21Z |
| format | Article |
| id | doaj.art-76519d2b242c4ed8a8347770af9e6382 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:42:21Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-76519d2b242c4ed8a8347770af9e63822022-12-21T22:59:25ZengNature PortfolioScientific Reports2045-23222021-06-0111111110.1038/s41598-021-91008-6Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathwayShujun Yang0Yaodong Song1Qiaofang Wang2Yanna Liu3Zhongwei Wu4Xiaojia Duan5Yan Zhang6Xiuqian Bi7Yuanzhang Geng8Sanyang Chen9Changju Zhu10Department of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Emergency, The First Affiliated Hospital of Zhengzhou UniversityAbstract Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of l-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)–signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2–STAT3 signalling.https://doi.org/10.1038/s41598-021-91008-6 |
| spellingShingle | Shujun Yang Yaodong Song Qiaofang Wang Yanna Liu Zhongwei Wu Xiaojia Duan Yan Zhang Xiuqian Bi Yuanzhang Geng Sanyang Chen Changju Zhu Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway Scientific Reports |
| title | Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway |
| title_full | Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway |
| title_fullStr | Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway |
| title_full_unstemmed | Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway |
| title_short | Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway |
| title_sort | daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the jak2 stat3 pathway |
| url | https://doi.org/10.1038/s41598-021-91008-6 |
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