Schisandrin A ameliorates increased pulmonary capillary endothelial permeability accompanied with sepsis through inhibition of RhoA/ROCK1/MLC pathways
Copyright © 2023 Elsevier B.V. All rights reserved..
BACKGROUND: Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown.
OBJECTIVE: To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis.
METHODS: The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot.
RESULTS: The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway.
CONCLUSION: In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
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| Enthalten in: |
International immunopharmacology - 118(2023) vom: 01. Mai, Seite 110124 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
You, Li-Juan [VerfasserIn] |
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| Links: |
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| Themen: |
74XQL5DO3S |
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| Anmerkungen: |
Date Completed 25.04.2023 Date Revised 20.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2023.110124 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM355329336 |
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| 100 | 1 | |a You, Li-Juan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Schisandrin A ameliorates increased pulmonary capillary endothelial permeability accompanied with sepsis through inhibition of RhoA/ROCK1/MLC pathways |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 25.04.2023 | ||
| 500 | |a Date Revised 20.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown | ||
| 520 | |a OBJECTIVE: To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis | ||
| 520 | |a METHODS: The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot | ||
| 520 | |a RESULTS: The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway | ||
| 520 | |a CONCLUSION: In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute lung injury | |
| 650 | 4 | |a RhoA/ROCK1/MLC | |
| 650 | 4 | |a Schisandrin A | |
| 650 | 4 | |a Vascular permeability | |
| 650 | 7 | |a schizandrin A |2 NLM | |
| 650 | 7 | |a 74XQL5DO3S |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a rho-Associated Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Lignans |2 NLM | |
| 650 | 7 | |a ROCK1 protein, rat |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Li, Pei-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wen-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Ming-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wei-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Hui-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Piao, Xian-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Li-Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yan |e verfasserin |4 aut | |
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