Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway
Hao-Ran Xu,1 Qian Yang,1 Shu-Yang Xiang,1 Pu-Hong Zhang,1 Yang Ye,1 Yan Chen,1 Ke-Wen Xu,2 Xi-Ya Ren,2 Hong-Xia Mei,1 Chen-Xi Shen,1 Hong-Yu Ma,1 Fang-Gao Smith,1,3 Sheng-Wei Jin,1 Qian Wang1 1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s H...
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Dove Medical Press
2021
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oai:doaj.org-article:d1b44b5143604d7eb1fc76f9de3012082021-12-02T18:03:16ZRosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway1178-7031https://doaj.org/article/d1b44b5143604d7eb1fc76f9de3012082021-04-01T00:00:00Zhttps://www.dovepress.com/rosuvastatin-enhances-alveolar-fluid-clearance-in-lipopolysaccharide-i-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Hao-Ran Xu,1 Qian Yang,1 Shu-Yang Xiang,1 Pu-Hong Zhang,1 Yang Ye,1 Yan Chen,1 Ke-Wen Xu,2 Xi-Ya Ren,2 Hong-Xia Mei,1 Chen-Xi Shen,1 Hong-Yu Ma,1 Fang-Gao Smith,1,3 Sheng-Wei Jin,1 Qian Wang1 1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKCorrespondence: Sheng-Wei Jin; Qian WangDepartment of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province, 325027, People’s Republic of ChinaTel +86 577-88002806Fax +86 577-88832693Email jsw@wmu.edu.cn; wqian84@163.comBackground: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects.Methods: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6– 8). Rosuvastatin (0.3 μmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h.Results: Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na,K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway.Conclusion: In summary, the findings of our study revealed the potential role of rosuvastatin in the management of ALI/ARDS.Keywords: acute respiratory distress syndrome, rosuvastatin, alveolar fluid clearance, sodium channel, Na,K-ATPasesXu HRYang QXiang SYZhang PHYe YChen YXu KWRen XYMei HXShen CXMa HYSmith FGJin SWWang QDove Medical Pressarticleacute respiratory distress syndromerosuvastatinalveolar fluid clearancesodium channelnak-atpasesPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 1537-1549 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
acute respiratory distress syndrome rosuvastatin alveolar fluid clearance sodium channel na k-atpases Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
acute respiratory distress syndrome rosuvastatin alveolar fluid clearance sodium channel na k-atpases Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Xu HR Yang Q Xiang SY Zhang PH Ye Y Chen Y Xu KW Ren XY Mei HX Shen CX Ma HY Smith FG Jin SW Wang Q Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway |
| description |
Hao-Ran Xu,1 Qian Yang,1 Shu-Yang Xiang,1 Pu-Hong Zhang,1 Yang Ye,1 Yan Chen,1 Ke-Wen Xu,2 Xi-Ya Ren,2 Hong-Xia Mei,1 Chen-Xi Shen,1 Hong-Yu Ma,1 Fang-Gao Smith,1,3 Sheng-Wei Jin,1 Qian Wang1 1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKCorrespondence: Sheng-Wei Jin; Qian WangDepartment of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province, 325027, People’s Republic of ChinaTel +86 577-88002806Fax +86 577-88832693Email jsw@wmu.edu.cn; wqian84@163.comBackground: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects.Methods: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6– 8). Rosuvastatin (0.3 μmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h.Results: Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na,K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway.Conclusion: In summary, the findings of our study revealed the potential role of rosuvastatin in the management of ALI/ARDS.Keywords: acute respiratory distress syndrome, rosuvastatin, alveolar fluid clearance, sodium channel, Na,K-ATPases |
| format |
article |
| author |
Xu HR Yang Q Xiang SY Zhang PH Ye Y Chen Y Xu KW Ren XY Mei HX Shen CX Ma HY Smith FG Jin SW Wang Q |
| author_facet |
Xu HR Yang Q Xiang SY Zhang PH Ye Y Chen Y Xu KW Ren XY Mei HX Shen CX Ma HY Smith FG Jin SW Wang Q |
| author_sort |
Xu HR |
| title |
Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway |
| title_short |
Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway |
| title_full |
Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway |
| title_fullStr |
Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway |
| title_full_unstemmed |
Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway |
| title_sort |
rosuvastatin enhances alveolar fluid clearance in lipopolysaccharide-induced acute lung injury by activating the expression of sodium channel and na,k-atpase via the pi3k/akt/nedd4-2 pathway |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/d1b44b5143604d7eb1fc76f9de301208 |
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