Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway
IntroductionIn patients with acute respiratory distress syndrome, mechanical ventilation often leads to ventilation-induced lung injury (VILI), which is attributed to unphysiological lung strain (UPLS) in respiratory dynamics. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1469783/full |
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| author | Gang Liu Gang Liu Bin-Bin Dong Bin-Bin Dong Zi-Heng Ding Zi-Heng Ding Chao Lan Chang-Ju Zhu Qi Liu Qi Liu |
| author_facet | Gang Liu Gang Liu Bin-Bin Dong Bin-Bin Dong Zi-Heng Ding Zi-Heng Ding Chao Lan Chang-Ju Zhu Qi Liu Qi Liu |
| author_sort | Gang Liu |
| collection | DOAJ |
| description | IntroductionIn patients with acute respiratory distress syndrome, mechanical ventilation often leads to ventilation-induced lung injury (VILI), which is attributed to unphysiological lung strain (UPLS) in respiratory dynamics. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane receptor, senses mechanical signals. The Src/STAT3 pathway plays a crucial role in the mechanotransduction network, concurrently triggering pyroptosis related inflammatory responses. We hypothesized that the mechanical stretch caused by UPLS can be sensed by PECAM-1 in the lungs, leading to VILI via the Src/STAT3 and pyroptosis pathway.MethodsA VILI model was established in rats through UPLS. The link between lung strain and VILI as well as the change in the activation of PECAM-1, Src/STAT3, and pyroptosis was firstly being explored. Then, the inhibitors of PECAM-1, Src, STAT3 were adopted respectively, the effect on VILI, inflammation, the Src/STAT3 pathway, and pyroptosis was evaluated. In vitro, human umbilical vein endothelial cells (HUVECs) were used to validate the findings in vivo.ResultsUPLS activated PECAM-1, Src/STAT3 signaling pathway, inflammation, and pyroptosis in the VILI model with rats, whereas inhibition of PECAM-1 or the Src/STAT3 signaling pathway decreased lung injury, inflammatory responses, and pyroptosis. Inhibition of PECAM-1 also reduced activation of the Src/STAT3 signaling pathway. The mechanism was validated with HUVECs exposed to overload mechanical cyclic stretch.ConclusionsThis study suggests that UPLS contributes to VILI by activating the PECAM-1/Src/STAT3 pathway and inducing inflammatory responses as well aspyroptosis. |
| format | Article |
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| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-e508a8984853440caf6e9e1d8251102e2025-08-20T01:48:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14697831469783Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathwayGang Liu0Gang Liu1Bin-Bin Dong2Bin-Bin Dong3Zi-Heng Ding4Zi-Heng Ding5Chao Lan6Chang-Ju Zhu7Qi Liu8Qi Liu9Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaTranslational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaTranslational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaTranslational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaTranslational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaIntroductionIn patients with acute respiratory distress syndrome, mechanical ventilation often leads to ventilation-induced lung injury (VILI), which is attributed to unphysiological lung strain (UPLS) in respiratory dynamics. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane receptor, senses mechanical signals. The Src/STAT3 pathway plays a crucial role in the mechanotransduction network, concurrently triggering pyroptosis related inflammatory responses. We hypothesized that the mechanical stretch caused by UPLS can be sensed by PECAM-1 in the lungs, leading to VILI via the Src/STAT3 and pyroptosis pathway.MethodsA VILI model was established in rats through UPLS. The link between lung strain and VILI as well as the change in the activation of PECAM-1, Src/STAT3, and pyroptosis was firstly being explored. Then, the inhibitors of PECAM-1, Src, STAT3 were adopted respectively, the effect on VILI, inflammation, the Src/STAT3 pathway, and pyroptosis was evaluated. In vitro, human umbilical vein endothelial cells (HUVECs) were used to validate the findings in vivo.ResultsUPLS activated PECAM-1, Src/STAT3 signaling pathway, inflammation, and pyroptosis in the VILI model with rats, whereas inhibition of PECAM-1 or the Src/STAT3 signaling pathway decreased lung injury, inflammatory responses, and pyroptosis. Inhibition of PECAM-1 also reduced activation of the Src/STAT3 signaling pathway. The mechanism was validated with HUVECs exposed to overload mechanical cyclic stretch.ConclusionsThis study suggests that UPLS contributes to VILI by activating the PECAM-1/Src/STAT3 pathway and inducing inflammatory responses as well aspyroptosis.https://www.frontiersin.org/articles/10.3389/fphar.2024.1469783/fullventilation-induced lung injuryunphysiological lung strainPECAM-1Src/STAT3pyroptosis |
| spellingShingle | Gang Liu Gang Liu Bin-Bin Dong Bin-Bin Dong Zi-Heng Ding Zi-Heng Ding Chao Lan Chang-Ju Zhu Qi Liu Qi Liu Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway Frontiers in Pharmacology ventilation-induced lung injury unphysiological lung strain PECAM-1 Src/STAT3 pyroptosis |
| title | Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway |
| title_full | Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway |
| title_fullStr | Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway |
| title_full_unstemmed | Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway |
| title_short | Unphysiological lung strain promotes ventilation-induced lung injury via activation of the PECAM-1/Src/STAT3 signaling pathway |
| title_sort | unphysiological lung strain promotes ventilation induced lung injury via activation of the pecam 1 src stat3 signaling pathway |
| topic | ventilation-induced lung injury unphysiological lung strain PECAM-1 Src/STAT3 pyroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1469783/full |
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