Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome
Abstract Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonanc...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01519-1 |
| _version_ | 1817994723717021696 |
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| author | ZhiZhi Qian QianYi Wang ZhaoShun Qiu DanYang Li ChenCheng Zhang XiYu Xiong ZiHui Zheng QinLi Ruan YiChen Guo Jun Guo |
| author_facet | ZhiZhi Qian QianYi Wang ZhaoShun Qiu DanYang Li ChenCheng Zhang XiYu Xiong ZiHui Zheng QinLi Ruan YiChen Guo Jun Guo |
| author_sort | ZhiZhi Qian |
| collection | DOAJ |
| description | Abstract Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonance energy transfer-based Intermediate filament (IF) tension optical probe. Angiotensin-II- and bradykinin-induced increases in intracellular protein nanoparticle (PN)-OP were associated with inflammasome production and cytoskeletal depolymerization. Intracellular protein nanoparticle production also resulted in cytomembrane hyperpolarization and L-VGCC-induced calcium signals, which differed from diacylglycerol-induced calcium increment via TRPC6 activation. Both pathways involve voltage-dependent cation influx and OP upregulation via SUR1-TRPM4 channels. Meanwhile, intra/extracellular PN-induced OP gradients across membranes upregulated pulmonary endothelial and alveolar barrier permeability. Attenuation of intracellular PN, calcium signals, and cation influx by drug combinations effectively relieved intracellular OP and pulmonary endothelial nonselective permeability, and improved epithelial fluid absorption and PE. Thus, PN-OP is pivotal in pulmonary edema in ARDS and COVID-19, and transmembrane OP recovery could be used to treat pulmonary edema and develop new drug targets in pulmonary injury. Graphical Abstract |
| first_indexed | 2024-04-14T01:55:57Z |
| format | Article |
| id | doaj.art-1fd73f22605b4f668483b5824d1bb7f3 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T01:55:57Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-1fd73f22605b4f668483b5824d1bb7f32022-12-22T02:19:04ZengBMCJournal of Nanobiotechnology1477-31552022-07-0120112110.1186/s12951-022-01519-1Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndromeZhiZhi Qian0QianYi Wang1ZhaoShun Qiu2DanYang Li3ChenCheng Zhang4XiYu Xiong5ZiHui Zheng6QinLi Ruan7YiChen Guo8Jun Guo9School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineBiomedical Engineering, University of Alabama at Birmingham School of MedicineSchool of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese MedicineAbstract Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonance energy transfer-based Intermediate filament (IF) tension optical probe. Angiotensin-II- and bradykinin-induced increases in intracellular protein nanoparticle (PN)-OP were associated with inflammasome production and cytoskeletal depolymerization. Intracellular protein nanoparticle production also resulted in cytomembrane hyperpolarization and L-VGCC-induced calcium signals, which differed from diacylglycerol-induced calcium increment via TRPC6 activation. Both pathways involve voltage-dependent cation influx and OP upregulation via SUR1-TRPM4 channels. Meanwhile, intra/extracellular PN-induced OP gradients across membranes upregulated pulmonary endothelial and alveolar barrier permeability. Attenuation of intracellular PN, calcium signals, and cation influx by drug combinations effectively relieved intracellular OP and pulmonary endothelial nonselective permeability, and improved epithelial fluid absorption and PE. Thus, PN-OP is pivotal in pulmonary edema in ARDS and COVID-19, and transmembrane OP recovery could be used to treat pulmonary edema and develop new drug targets in pulmonary injury. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01519-1ARDSPulmonary edemaProtein nanoparticle-induced osmotic pressureVoltage-dependent ion channelsMulti-targeted blockade |
| spellingShingle | ZhiZhi Qian QianYi Wang ZhaoShun Qiu DanYang Li ChenCheng Zhang XiYu Xiong ZiHui Zheng QinLi Ruan YiChen Guo Jun Guo Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome Journal of Nanobiotechnology ARDS Pulmonary edema Protein nanoparticle-induced osmotic pressure Voltage-dependent ion channels Multi-targeted blockade |
| title | Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome |
| title_full | Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome |
| title_fullStr | Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome |
| title_full_unstemmed | Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome |
| title_short | Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome |
| title_sort | protein nanoparticle induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome |
| topic | ARDS Pulmonary edema Protein nanoparticle-induced osmotic pressure Voltage-dependent ion channels Multi-targeted blockade |
| url | https://doi.org/10.1186/s12951-022-01519-1 |
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