Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice
Dan Chen,1,* Zhi-qi Gao,1,* Ying-ying Wang,1 Bin-bin Wan,1 Gang Liu,1 Jun-liang Chen,1 Ya-xian Wu,1 Qin Zhou,2 Shan-yu Jiang,2 Ren-qiang Yu,2 Qing-feng Pang1 1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People’s Republic of C...
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Dove Medical Press
2021
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oai:doaj.org-article:1215a5f3d74d426e916c6dfbe15d4a042021-12-02T14:20:30ZSodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice1178-7031https://doaj.org/article/1215a5f3d74d426e916c6dfbe15d4a042021-03-01T00:00:00Zhttps://www.dovepress.com/sodium-propionate-enhances-nrf2-mediated-protective-defense-against-ox-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Dan Chen,1,* Zhi-qi Gao,1,* Ying-ying Wang,1 Bin-bin Wan,1 Gang Liu,1 Jun-liang Chen,1 Ya-xian Wu,1 Qin Zhou,2 Shan-yu Jiang,2 Ren-qiang Yu,2 Qing-feng Pang1 1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People’s Republic of China; 2Department of Neonatology, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ren-qiang Yu 48 Huaishu Lane, Liangxi District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +86510-82709790Fax +86-510-82725094Email yurenqiang553@163.comQing-feng Pang 1800 Lihu Avenue, Binhu District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +8651052430172Fax +86-510-85329042Email qfpang@jiangnan.edu.cnBackground: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.Methods: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.Results: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.Conclusion: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.Keywords: sodium propionate, lipopolysaccharide, Nrf2, angiogenesis, bronchopulmonary dysplasiaChen DGao ZWang YWan BLiu GChen JWu YZhou QJiang SYu RPang QDove Medical Pressarticlesodium propionatelipopolysaccharidenrf2angiogenesisbronchopulmonary dysplasiaPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 803-816 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
sodium propionate lipopolysaccharide nrf2 angiogenesis bronchopulmonary dysplasia Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
sodium propionate lipopolysaccharide nrf2 angiogenesis bronchopulmonary dysplasia Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Chen D Gao Z Wang Y Wan B Liu G Chen J Wu Y Zhou Q Jiang S Yu R Pang Q Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice |
| description |
Dan Chen,1,* Zhi-qi Gao,1,* Ying-ying Wang,1 Bin-bin Wan,1 Gang Liu,1 Jun-liang Chen,1 Ya-xian Wu,1 Qin Zhou,2 Shan-yu Jiang,2 Ren-qiang Yu,2 Qing-feng Pang1 1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People’s Republic of China; 2Department of Neonatology, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ren-qiang Yu 48 Huaishu Lane, Liangxi District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +86510-82709790Fax +86-510-82725094Email yurenqiang553@163.comQing-feng Pang 1800 Lihu Avenue, Binhu District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +8651052430172Fax +86-510-85329042Email qfpang@jiangnan.edu.cnBackground: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.Methods: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.Results: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.Conclusion: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.Keywords: sodium propionate, lipopolysaccharide, Nrf2, angiogenesis, bronchopulmonary dysplasia |
| format |
article |
| author |
Chen D Gao Z Wang Y Wan B Liu G Chen J Wu Y Zhou Q Jiang S Yu R Pang Q |
| author_facet |
Chen D Gao Z Wang Y Wan B Liu G Chen J Wu Y Zhou Q Jiang S Yu R Pang Q |
| author_sort |
Chen D |
| title |
Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice |
| title_short |
Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice |
| title_full |
Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice |
| title_fullStr |
Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice |
| title_full_unstemmed |
Sodium Propionate Enhances Nrf2-Mediated Protective Defense Against Oxidative Stress and Inflammation in Lipopolysaccharide-Induced Neonatal Mice |
| title_sort |
sodium propionate enhances nrf2-mediated protective defense against oxidative stress and inflammation in lipopolysaccharide-induced neonatal mice |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/1215a5f3d74d426e916c6dfbe15d4a04 |
| work_keys_str_mv |
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1718391531242520576 |