PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury
Accidental exposure to phosgene can cause acute lung injury (ALI), characterized by uncontrolled inflammation and impaired lung blood-gas barrier. CD34+CD45+ cells with high pituitary tumor transforming gene 1 (PTTG1) expression were identified around rat pulmonary vessels through single-cell RNA se...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223004420 |
| _version_ | 1797837169307418624 |
|---|---|
| author | Yu Dun Hanbing Hu Fuli Liu Yiru Shao Daikun He Lin Zhang Jie Shen |
| author_facet | Yu Dun Hanbing Hu Fuli Liu Yiru Shao Daikun He Lin Zhang Jie Shen |
| author_sort | Yu Dun |
| collection | DOAJ |
| description | Accidental exposure to phosgene can cause acute lung injury (ALI), characterized by uncontrolled inflammation and impaired lung blood-gas barrier. CD34+CD45+ cells with high pituitary tumor transforming gene 1 (PTTG1) expression were identified around rat pulmonary vessels through single-cell RNA sequencing, and have been shown to attenuate P-ALI by promoting lung vascular barrier repair. As a transcription factor closely related to angiogenesis, whether PTTG1 plays a role in CD34+CD45+ cell repairing the pulmonary vascular barrier in rats with P-ALI remains unclear. This study provided compelling evidence that CD34+CD45+ cells possess endothelial differentiation potential. Rats with P-ALI were intratracheally administered with CD34+CD45+ cells transfected with or without PTTG1-overexpressing and sh-PTTG1 lentivirus. It was found that CD34+CD45+ cells reduced the pulmonary vascular permeability and mitigated the lung inflammation, which could be reversed by knocking down PTTG1. Although PTTG1 overexpression enhanced the ability of CD34+CD45+ cells to attenuate P-ALI, no significant difference was found. PTTG1 was found to regulate the endothelial differentiation of CD34+CD45+ cells. In addition, knocking down of PTTG1 significantly reduced the protein levels of VEGF and bFGF, as well as their receptors, which in turn inhibited the activation of the PI3K/AKT/eNOS signaling pathway in CD34+CD45+ cells. Moreover, LY294002 (PI3K inhibitor) treatment inhibited the endothelial differentiation of CD34+CD45+ cells, while SC79 (AKT activator) yielded the opposite effect. These findings suggest that PTTG1 can promote the endothelial differentiation of CD34+CD45+ cells by activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway, leading to the repair of the pulmonary vascular barrier in rats with P-ALI. |
| first_indexed | 2024-04-09T15:20:30Z |
| format | Article |
| id | doaj.art-7f84deba6bf34a20956f58d125bb4469 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T15:20:30Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-7f84deba6bf34a20956f58d125bb44692023-04-29T14:46:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-06-01162114654PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injuryYu Dun0Hanbing Hu1Fuli Liu2Yiru Shao3Daikun He4Lin Zhang5Jie Shen6Center of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, ChinaCenter of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, ChinaCenter of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, ChinaCenter of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, ChinaCenter of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, ChinaCenter of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, ChinaCenter of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China; Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, China; Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, China; Corresponding author at: Center of Emergency and Critical Medicine, Jinshan Hospital of Fudan University, China.Accidental exposure to phosgene can cause acute lung injury (ALI), characterized by uncontrolled inflammation and impaired lung blood-gas barrier. CD34+CD45+ cells with high pituitary tumor transforming gene 1 (PTTG1) expression were identified around rat pulmonary vessels through single-cell RNA sequencing, and have been shown to attenuate P-ALI by promoting lung vascular barrier repair. As a transcription factor closely related to angiogenesis, whether PTTG1 plays a role in CD34+CD45+ cell repairing the pulmonary vascular barrier in rats with P-ALI remains unclear. This study provided compelling evidence that CD34+CD45+ cells possess endothelial differentiation potential. Rats with P-ALI were intratracheally administered with CD34+CD45+ cells transfected with or without PTTG1-overexpressing and sh-PTTG1 lentivirus. It was found that CD34+CD45+ cells reduced the pulmonary vascular permeability and mitigated the lung inflammation, which could be reversed by knocking down PTTG1. Although PTTG1 overexpression enhanced the ability of CD34+CD45+ cells to attenuate P-ALI, no significant difference was found. PTTG1 was found to regulate the endothelial differentiation of CD34+CD45+ cells. In addition, knocking down of PTTG1 significantly reduced the protein levels of VEGF and bFGF, as well as their receptors, which in turn inhibited the activation of the PI3K/AKT/eNOS signaling pathway in CD34+CD45+ cells. Moreover, LY294002 (PI3K inhibitor) treatment inhibited the endothelial differentiation of CD34+CD45+ cells, while SC79 (AKT activator) yielded the opposite effect. These findings suggest that PTTG1 can promote the endothelial differentiation of CD34+CD45+ cells by activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway, leading to the repair of the pulmonary vascular barrier in rats with P-ALI.http://www.sciencedirect.com/science/article/pii/S0753332223004420CD34+CD45+ cellsPTTG1Endothelial differentiationPulmonary vascular barrierPhosgeneVEGF-bFGF/PI3K/AKT/eNOS signaling pathway |
| spellingShingle | Yu Dun Hanbing Hu Fuli Liu Yiru Shao Daikun He Lin Zhang Jie Shen PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury Biomedicine & Pharmacotherapy CD34+CD45+ cells PTTG1 Endothelial differentiation Pulmonary vascular barrier Phosgene VEGF-bFGF/PI3K/AKT/eNOS signaling pathway |
| title | PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury |
| title_full | PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury |
| title_fullStr | PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury |
| title_full_unstemmed | PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury |
| title_short | PTTG1 promotes CD34+CD45+ cells to repair the pulmonary vascular barrier via activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway in rats with phosgene-induced acute lung injury |
| title_sort | pttg1 promotes cd34 cd45 cells to repair the pulmonary vascular barrier via activating the vegf bfgf pi3k akt enos signaling pathway in rats with phosgene induced acute lung injury |
| topic | CD34+CD45+ cells PTTG1 Endothelial differentiation Pulmonary vascular barrier Phosgene VEGF-bFGF/PI3K/AKT/eNOS signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223004420 |
| work_keys_str_mv | AT yudun pttg1promotescd34cd45cellstorepairthepulmonaryvascularbarrierviaactivatingthevegfbfgfpi3kaktenossignalingpathwayinratswithphosgeneinducedacutelunginjury AT hanbinghu pttg1promotescd34cd45cellstorepairthepulmonaryvascularbarrierviaactivatingthevegfbfgfpi3kaktenossignalingpathwayinratswithphosgeneinducedacutelunginjury AT fuliliu pttg1promotescd34cd45cellstorepairthepulmonaryvascularbarrierviaactivatingthevegfbfgfpi3kaktenossignalingpathwayinratswithphosgeneinducedacutelunginjury AT yirushao pttg1promotescd34cd45cellstorepairthepulmonaryvascularbarrierviaactivatingthevegfbfgfpi3kaktenossignalingpathwayinratswithphosgeneinducedacutelunginjury AT daikunhe pttg1promotescd34cd45cellstorepairthepulmonaryvascularbarrierviaactivatingthevegfbfgfpi3kaktenossignalingpathwayinratswithphosgeneinducedacutelunginjury AT linzhang pttg1promotescd34cd45cellstorepairthepulmonaryvascularbarrierviaactivatingthevegfbfgfpi3kaktenossignalingpathwayinratswithphosgeneinducedacutelunginjury AT jieshen pttg1promotescd34cd45cellstorepairthepulmonaryvascularbarrierviaactivatingthevegfbfgfpi3kaktenossignalingpathwayinratswithphosgeneinducedacutelunginjury |