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Published in: BMC Pulmonary Medicine 1/2019

Open Access 01-12-2019 | Smoking and Nicotine Detoxification | Research article

Ursolic acid alleviates airway-vessel remodeling and muscle consumption in cigarette smoke-induced emphysema rats

Authors: Li Lin, Gang Hou, Dan Han, Yan Yin, Jian Kang, Qiuyue Wang

Published in: BMC Pulmonary Medicine | Issue 1/2019

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Abstract

Background

This study assessed the effects of ursolic acid (UA) on airway-vessel remodeling and muscle atrophy in cigarette smoke (CS)-induced emphysema rats and investigated potential underlying mechanisms.

Methods

Emphysema was induced in a rat model with 3 months of CS exposure. Histology and immunohistochemistry (IHC) stains were used to assess airway-vessel remodeling and muscle atrophy-associated changes. Levels of cleaved-caspase3, 8-OHdG, and S100A4 were measured in airways and associated vessels to evaluate cell apoptosis, oxidant stress, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT)-associated factors. Western blot and/or IHC analyses were performed to measure transforming growth factor-beta 1(TGF-β1)/Smad2.3, alpha-smooth muscle actin (α-SMA), and insulin-like growth factor 1 (IGF1) expression. We also gave cultured HBE and HUVEC cells Cigarette Smoke Extract (CSE) administration and UA intervention. Using Western blot method to measure TGF-β1/Smad2.3, α-SMA, S100A4, and IGF1 molecules expression.

Results

UA decreased oxidant stress and cell apoptosis in airway and accompanying vascular walls of cigarette smoke-induced emphysema model rats. UA alleviated EMT, EndMT, changes associated with airway-vessel remodeling and muscle atrophy. The UA effects were associated with IGF1 and TGF-β1/Smad2.3 pathways.

Conclusions

UA reduced EMT, EndMT, airway-vessel remodeling, and musculi soleus atrophy in CS-induced emphysema model rats at least partly through IGF1 and TGF-β1/Smad2.3 signaling pathways.
Literature
1.
go back to reference Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, Menezes AM, Sullivan SD, Lee TA, Weiss KB, et al. International variation in the prevalence of COPD (the BOLD study): a population-based prevalence study. Lancet. 2007;370(9589):741–50.PubMedCrossRef Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, Menezes AM, Sullivan SD, Lee TA, Weiss KB, et al. International variation in the prevalence of COPD (the BOLD study): a population-based prevalence study. Lancet. 2007;370(9589):741–50.PubMedCrossRef
2.
go back to reference Wang C, Xu J, Yang L, Xu Y, Zhang X, Bai C, Kang J, Ran P, Shen H, Wen F, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China pulmonary health [CPH] study): a national cross-sectional study. Lancet. 2018;391(10131):1706–17.PubMedCrossRef Wang C, Xu J, Yang L, Xu Y, Zhang X, Bai C, Kang J, Ran P, Shen H, Wen F, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China pulmonary health [CPH] study): a national cross-sectional study. Lancet. 2018;391(10131):1706–17.PubMedCrossRef
3.
go back to reference T O, K N, M T, S S. T H: analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status. Am J Respir Crit Care Med. 2003;167(4):544–9.CrossRef T O, K N, M T, S S. T H: analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status. Am J Respir Crit Care Med. 2003;167(4):544–9.CrossRef
4.
go back to reference Zhong N, Wang C, Yao W, Chen P, Kang J, Huang S, Chen B, Wang C, Ni D, Zhou Y, et al. Prevalence of chronic obstructive pulmonary disease in China: a large, population-based survey. Am J Respir Crit Care Med. 2007;176(8):753–60.PubMedCrossRef Zhong N, Wang C, Yao W, Chen P, Kang J, Huang S, Chen B, Wang C, Ni D, Zhou Y, et al. Prevalence of chronic obstructive pulmonary disease in China: a large, population-based survey. Am J Respir Crit Care Med. 2007;176(8):753–60.PubMedCrossRef
5.
go back to reference Oga T, Nishimura K, Tsukino M, Sato S, Hajiro T. Analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status. Am J Respir Crit Care Med. 2003;167(4):544–9.PubMedCrossRef Oga T, Nishimura K, Tsukino M, Sato S, Hajiro T. Analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status. Am J Respir Crit Care Med. 2003;167(4):544–9.PubMedCrossRef
6.
go back to reference McMillan DH, Baglole CJ, Thatcher TH, Maggirwar S, Sime PJ, Phipps RP. Lung-targeted overexpression of the NF-kappaB member RelB inhibits cigarette smoke-induced inflammation. Am J Pathol. 2011;179(1):125–33.PubMedPubMedCentralCrossRef McMillan DH, Baglole CJ, Thatcher TH, Maggirwar S, Sime PJ, Phipps RP. Lung-targeted overexpression of the NF-kappaB member RelB inhibits cigarette smoke-induced inflammation. Am J Pathol. 2011;179(1):125–33.PubMedPubMedCentralCrossRef
7.
go back to reference Gould NS, Min E, Gauthier S, Chu HW, Martin R, Day BJ. Aging adversely affects the cigarette smoke-induced glutathione adaptive response in the lung. Am J Respir Crit Care Med. 2010;182(9):1114–22.PubMedPubMedCentralCrossRef Gould NS, Min E, Gauthier S, Chu HW, Martin R, Day BJ. Aging adversely affects the cigarette smoke-induced glutathione adaptive response in the lung. Am J Respir Crit Care Med. 2010;182(9):1114–22.PubMedPubMedCentralCrossRef
8.
go back to reference Soltani A, Walters EH, Reid DW, Shukla SD, Nowrin K, Ward C, Muller HK, Sohal SS. Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD. International journal of chronic obstructive pulmonary disease. 2016;11:2359–67.PubMedPubMedCentralCrossRef Soltani A, Walters EH, Reid DW, Shukla SD, Nowrin K, Ward C, Muller HK, Sohal SS. Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD. International journal of chronic obstructive pulmonary disease. 2016;11:2359–67.PubMedPubMedCentralCrossRef
9.
go back to reference Baddini-Martinez J, de Padua AI. Chronic obstructive pulmonary disease: time to discuss new concepts. Lancet. 2016;388(10061):2740–1.PubMedCrossRef Baddini-Martinez J, de Padua AI. Chronic obstructive pulmonary disease: time to discuss new concepts. Lancet. 2016;388(10061):2740–1.PubMedCrossRef
10.
go back to reference Barreiro E, Gea J. Molecular and biological pathways of skeletal muscle dysfunction in chronic obstructive pulmonary disease. Chronic respiratory disease. 2016;13(3):297–311.PubMedPubMedCentralCrossRef Barreiro E, Gea J. Molecular and biological pathways of skeletal muscle dysfunction in chronic obstructive pulmonary disease. Chronic respiratory disease. 2016;13(3):297–311.PubMedPubMedCentralCrossRef
11.
go back to reference Blanco I, Piccari L, Barbera JA. Pulmonary vasculature in COPD: the silent component. Respirology (Carlton, Vic). 2016;21(6):984–94.CrossRef Blanco I, Piccari L, Barbera JA. Pulmonary vasculature in COPD: the silent component. Respirology (Carlton, Vic). 2016;21(6):984–94.CrossRef
12.
go back to reference Costa TM, Costa FM, Moreira CA, Rabelo LM, Boguszewski CL, Borba VZ. Sarcopenia in COPD: relationship with COPD severity and prognosis. Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 2015;41(5):415–21.CrossRef Costa TM, Costa FM, Moreira CA, Rabelo LM, Boguszewski CL, Borba VZ. Sarcopenia in COPD: relationship with COPD severity and prognosis. Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 2015;41(5):415–21.CrossRef
13.
go back to reference Pera T, Zuidhof AB, Smit M, Menzen MH, Klein T, Flik G, Zaagsma J, Meurs H, Maarsingh H. Arginase inhibition prevents inflammation and remodeling in a Guinea pig model of chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2014;349(2):229–38.PubMedCrossRef Pera T, Zuidhof AB, Smit M, Menzen MH, Klein T, Flik G, Zaagsma J, Meurs H, Maarsingh H. Arginase inhibition prevents inflammation and remodeling in a Guinea pig model of chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2014;349(2):229–38.PubMedCrossRef
14.
go back to reference Alagappan VK, de Boer WI, Misra VK, Mooi WJ, Sharma HS. Angiogenesis and vascular remodeling in chronic airway diseases. Cell Biochem Biophys. 2013;67(2):219–34.PubMedCrossRef Alagappan VK, de Boer WI, Misra VK, Mooi WJ, Sharma HS. Angiogenesis and vascular remodeling in chronic airway diseases. Cell Biochem Biophys. 2013;67(2):219–34.PubMedCrossRef
15.
go back to reference Sohal SS. Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD). Respir Investig. 2017;55(2):104–13.PubMedCrossRef Sohal SS. Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD). Respir Investig. 2017;55(2):104–13.PubMedCrossRef
16.
go back to reference Sohal S. Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD). Respir Investig. 2017;55(2):104–13.PubMedCrossRef Sohal S. Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD). Respir Investig. 2017;55(2):104–13.PubMedCrossRef
17.
19.
go back to reference Takayanagi S, Kawata N, Tada Y, Ikari J, Matsuura Y, Matsuoka S, Matsushita S, Yanagawa N, Kasahara Y, Tatsumi K. Longitudinal changes in structural abnormalities using MDCT in COPD: do the CT measurements of airway wall thickness and small pulmonary vessels change in parallel with emphysematous progression? Int J Chron Obstruct Pulmon Dis. 2017;12:551–60.PubMedPubMedCentralCrossRef Takayanagi S, Kawata N, Tada Y, Ikari J, Matsuura Y, Matsuoka S, Matsushita S, Yanagawa N, Kasahara Y, Tatsumi K. Longitudinal changes in structural abnormalities using MDCT in COPD: do the CT measurements of airway wall thickness and small pulmonary vessels change in parallel with emphysematous progression? Int J Chron Obstruct Pulmon Dis. 2017;12:551–60.PubMedPubMedCentralCrossRef
20.
go back to reference Fathy E, Shafiek H, Morsi T, El Sabaa B, Elnekidy A, Elhoffy M, Atta M. Image-enhanced bronchoscopic evaluation of bronchial mucosal microvasculature in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2447–55.CrossRef Fathy E, Shafiek H, Morsi T, El Sabaa B, Elnekidy A, Elhoffy M, Atta M. Image-enhanced bronchoscopic evaluation of bronchial mucosal microvasculature in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2447–55.CrossRef
21.
go back to reference Soltani A, Walters E, Reid D, Shukla S, Nowrin K, Ward C, Muller H, Sohal S. Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2359–67.PubMedPubMedCentralCrossRef Soltani A, Walters E, Reid D, Shukla S, Nowrin K, Ward C, Muller H, Sohal S. Inhaled corticosteroid normalizes some but not all airway vascular remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2359–67.PubMedPubMedCentralCrossRef
22.
go back to reference Harkness L, Kanabar V, Sharma H, Westergren-Thorsson G, Larsson-Callerfelt A. Pulmonary vascular changes in asthma and COPD. Pulm Pharmacol Ther. 2014;29(2):144–55.PubMedCrossRef Harkness L, Kanabar V, Sharma H, Westergren-Thorsson G, Larsson-Callerfelt A. Pulmonary vascular changes in asthma and COPD. Pulm Pharmacol Ther. 2014;29(2):144–55.PubMedCrossRef
23.
go back to reference Seeger W, Adir Y, Barberà J, Champion H, Coghlan J, Cottin V, De Marco T, Galiè N, Ghio S, Gibbs S, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D109–16.PubMedCrossRef Seeger W, Adir Y, Barberà J, Champion H, Coghlan J, Cottin V, De Marco T, Galiè N, Ghio S, Gibbs S, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D109–16.PubMedCrossRef
24.
go back to reference Khanna A, Guo M, Mehra M, Royal W. Inflammation and oxidative stress induced by cigarette smoke in Lewis rat brains. J Neuroimmunol. 2013;254(1–2):69–75.PubMedCrossRef Khanna A, Guo M, Mehra M, Royal W. Inflammation and oxidative stress induced by cigarette smoke in Lewis rat brains. J Neuroimmunol. 2013;254(1–2):69–75.PubMedCrossRef
25.
go back to reference Lunghi B, De Cunto G, Cavarra E, Fineschi S, Bartalesi B, Lungarella G, Lucattelli M. Smoking p66Shc knocked out mice develop respiratory bronchiolitis with fibrosis but not emphysema. PLoS One. 2015;10(3):e0119797.PubMedPubMedCentralCrossRef Lunghi B, De Cunto G, Cavarra E, Fineschi S, Bartalesi B, Lungarella G, Lucattelli M. Smoking p66Shc knocked out mice develop respiratory bronchiolitis with fibrosis but not emphysema. PLoS One. 2015;10(3):e0119797.PubMedPubMedCentralCrossRef
26.
go back to reference Richardson L, Dixon C, Aguilera-Aguirre L, Menon R. Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells. Biol Reprod. 2018. Richardson L, Dixon C, Aguilera-Aguirre L, Menon R. Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells. Biol Reprod. 2018.
27.
go back to reference Chen H, Liao K, Cui-Zhao L, Qiang-Wen F, Feng-Zeng X, Ping-Wu F, Liang-Guo S, Juan-Chen Y. Cigarette smoke extract induces apoptosis of rat alveolar type II cells via the PLTP/TGF-β1/Smad2 pathway. Int Immunopharmacol. 2015;28(1):707–14.PubMedCrossRef Chen H, Liao K, Cui-Zhao L, Qiang-Wen F, Feng-Zeng X, Ping-Wu F, Liang-Guo S, Juan-Chen Y. Cigarette smoke extract induces apoptosis of rat alveolar type II cells via the PLTP/TGF-β1/Smad2 pathway. Int Immunopharmacol. 2015;28(1):707–14.PubMedCrossRef
28.
go back to reference Mahmood MQ, Reid D, Ward C, Muller HK, Knight DA, Sohal SS, Walters EH. Transforming growth factor (TGF) beta1 and Smad signalling pathways: a likely key to EMT-associated COPD pathogenesis. Respirology (Carlton, Vic). 2017;22(1):133–40.CrossRef Mahmood MQ, Reid D, Ward C, Muller HK, Knight DA, Sohal SS, Walters EH. Transforming growth factor (TGF) beta1 and Smad signalling pathways: a likely key to EMT-associated COPD pathogenesis. Respirology (Carlton, Vic). 2017;22(1):133–40.CrossRef
29.
go back to reference Guan S, Liu Q, Han F, Gu W, Song L, Zhang Y, Guo X, Xu W. Ginsenoside Rg1 ameliorates cigarette smoke-induced airway fibrosis by suppressing the TGF-beta1/Smad pathway in vivo and in vitro. Biomed Res Int. 2017;2017:6510198.PubMedPubMedCentral Guan S, Liu Q, Han F, Gu W, Song L, Zhang Y, Guo X, Xu W. Ginsenoside Rg1 ameliorates cigarette smoke-induced airway fibrosis by suppressing the TGF-beta1/Smad pathway in vivo and in vitro. Biomed Res Int. 2017;2017:6510198.PubMedPubMedCentral
30.
go back to reference Soltani A, Sohal SS, Reid D, Weston S, Wood-Baker R, Walters EH. Vessel-associated transforming growth factor-beta1 (TGF-beta1) is increased in the bronchial reticular basement membrane in COPD and normal smokers. PLoS One. 2012;7(6):e39736.PubMedPubMedCentralCrossRef Soltani A, Sohal SS, Reid D, Weston S, Wood-Baker R, Walters EH. Vessel-associated transforming growth factor-beta1 (TGF-beta1) is increased in the bronchial reticular basement membrane in COPD and normal smokers. PLoS One. 2012;7(6):e39736.PubMedPubMedCentralCrossRef
31.
go back to reference Ichimaru Y, Krimmer DI, Burgess JK, Black JL, Oliver BG. TGF-beta enhances deposition of perlecan from COPD airway smooth muscle. American journal of physiology Lung cellular and molecular physiology. 2012;302(3):L325–33.PubMedCrossRef Ichimaru Y, Krimmer DI, Burgess JK, Black JL, Oliver BG. TGF-beta enhances deposition of perlecan from COPD airway smooth muscle. American journal of physiology Lung cellular and molecular physiology. 2012;302(3):L325–33.PubMedCrossRef
32.
go back to reference Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet. 2004;364(9435):709–21.PubMedCrossRef Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet. 2004;364(9435):709–21.PubMedCrossRef
33.
34.
go back to reference Kranenburg AR, de Boer WI, Alagappan VK, Sterk PJ, Sharma HS. Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(2):106–13.PubMedPubMedCentralCrossRef Kranenburg AR, de Boer WI, Alagappan VK, Sterk PJ, Sharma HS. Enhanced bronchial expression of vascular endothelial growth factor and receptors (Flk-1 and Flt-1) in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(2):106–13.PubMedPubMedCentralCrossRef
35.
go back to reference Tanimura K, Sato S, Fuseya Y, Hasegawa K, Uemasu K, Sato A, Oguma T, Hirai T, Mishima M, Muro S. Quantitative assessment of erector spinae muscles in patients with chronic obstructive pulmonary disease. Novel chest computed tomography-derived index for prognosis. Annals of the American Thoracic Society. 2016;13(3):334–41.PubMedCrossRef Tanimura K, Sato S, Fuseya Y, Hasegawa K, Uemasu K, Sato A, Oguma T, Hirai T, Mishima M, Muro S. Quantitative assessment of erector spinae muscles in patients with chronic obstructive pulmonary disease. Novel chest computed tomography-derived index for prognosis. Annals of the American Thoracic Society. 2016;13(3):334–41.PubMedCrossRef
36.
go back to reference Pansters NA, Langen RC, Wouters EF, Schols AM. Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling. Journal of applied physiology (Bethesda, Md : 1985). 2013;114(9):1329–39.CrossRef Pansters NA, Langen RC, Wouters EF, Schols AM. Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling. Journal of applied physiology (Bethesda, Md : 1985). 2013;114(9):1329–39.CrossRef
37.
go back to reference Lopez IP, Pineiro-Hermida S, Pais RS, Torrens R, Hoeflich A, Pichel JG. Involvement of Igf1r in bronchiolar epithelial regeneration: role during repair kinetics after selective Club cell ablation. PLoS One. 2016;11(11):e0166388.PubMedPubMedCentralCrossRef Lopez IP, Pineiro-Hermida S, Pais RS, Torrens R, Hoeflich A, Pichel JG. Involvement of Igf1r in bronchiolar epithelial regeneration: role during repair kinetics after selective Club cell ablation. PLoS One. 2016;11(11):e0166388.PubMedPubMedCentralCrossRef
38.
go back to reference Ma R, Gong X, Jiang H, Lin C, Chen Y, Xu X, Zhang C, Wang J, Lu W, Zhong N. Reduced nuclear translocation of serum response factor is associated with skeletal muscle atrophy in a cigarette smoke-induced mouse model of COPD. International journal of chronic obstructive pulmonary disease. 2017;12:581–7.PubMedPubMedCentralCrossRef Ma R, Gong X, Jiang H, Lin C, Chen Y, Xu X, Zhang C, Wang J, Lu W, Zhong N. Reduced nuclear translocation of serum response factor is associated with skeletal muscle atrophy in a cigarette smoke-induced mouse model of COPD. International journal of chronic obstructive pulmonary disease. 2017;12:581–7.PubMedPubMedCentralCrossRef
39.
go back to reference Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, Bouillon R, Decramer M. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax. 2003;58(9):752–6.PubMedPubMedCentralCrossRef Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, Bouillon R, Decramer M. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax. 2003;58(9):752–6.PubMedPubMedCentralCrossRef
40.
go back to reference Ding H, Wang H, Zhu L, Wei W. Ursolic acid ameliorates early brain injury after experimental traumatic brain injury in mice by activating the Nrf2 pathway. Neurochem Res. 2016. Ding H, Wang H, Zhu L, Wei W. Ursolic acid ameliorates early brain injury after experimental traumatic brain injury in mice by activating the Nrf2 pathway. Neurochem Res. 2016.
41.
go back to reference Rai SN, Yadav SK, Singh D, Singh SP. Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced parkinsonian mouse model. J Chem Neuroanat. 2016;71:41–9.PubMedCrossRef Rai SN, Yadav SK, Singh D, Singh SP. Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced parkinsonian mouse model. J Chem Neuroanat. 2016;71:41–9.PubMedCrossRef
42.
go back to reference Kashyap D, Sharma A, Tuli HS, Punia S, Sharma AK. Ursolic acid and Oleanolic acid: Pentacyclic Terpenoids with promising anti-inflammatory activities. Recent Patents Inflamm Allergy Drug Discov. 2016;10(1):21–33.CrossRef Kashyap D, Sharma A, Tuli HS, Punia S, Sharma AK. Ursolic acid and Oleanolic acid: Pentacyclic Terpenoids with promising anti-inflammatory activities. Recent Patents Inflamm Allergy Drug Discov. 2016;10(1):21–33.CrossRef
43.
go back to reference Wang S, Meng X, Dong Y. Ursolic acid nanoparticles inhibit cervical cancer growth in vitro and in vivo via apoptosis induction. Int J Oncol. 2017;50(4):1330–40.PubMedCrossRef Wang S, Meng X, Dong Y. Ursolic acid nanoparticles inhibit cervical cancer growth in vitro and in vivo via apoptosis induction. Int J Oncol. 2017;50(4):1330–40.PubMedCrossRef
44.
go back to reference Yang Y, Li C, Xiang X, Dai Z, Chang J, Zhang M, Cai H, Zhang H, Zhang M, Guo Y, et al. Ursolic acid prevents endoplasmic reticulum stress-mediated apoptosis induced by heat stress in mouse cardiac myocytes. J Mol Cell Cardiol. 2014;67:103–11.PubMedCrossRef Yang Y, Li C, Xiang X, Dai Z, Chang J, Zhang M, Cai H, Zhang H, Zhang M, Guo Y, et al. Ursolic acid prevents endoplasmic reticulum stress-mediated apoptosis induced by heat stress in mouse cardiac myocytes. J Mol Cell Cardiol. 2014;67:103–11.PubMedCrossRef
45.
go back to reference Dong X, Liu S, Zhang L, Yu S, Huo L, Qile M, Liu L, Yang B, Yu J. Downregulation of miR-21 is involved in direct actions of ursolic acid on the heart: implications for cardiac fibrosis and hypertrophy. Cardiovasc Ther. 2015;33(4):161–7.PubMedCrossRef Dong X, Liu S, Zhang L, Yu S, Huo L, Qile M, Liu L, Yang B, Yu J. Downregulation of miR-21 is involved in direct actions of ursolic acid on the heart: implications for cardiac fibrosis and hypertrophy. Cardiovasc Ther. 2015;33(4):161–7.PubMedCrossRef
46.
go back to reference Lin L, Yin Y, Hou G, Han D, Kang J, Wang Q. Ursolic acid attenuates cigarette smoke-induced emphysema in rats by regulating PERK and Nrf2 pathways. Pulm Pharmacol Ther. 2017;44:111–21.PubMedCrossRef Lin L, Yin Y, Hou G, Han D, Kang J, Wang Q. Ursolic acid attenuates cigarette smoke-induced emphysema in rats by regulating PERK and Nrf2 pathways. Pulm Pharmacol Ther. 2017;44:111–21.PubMedCrossRef
47.
go back to reference Murakami S, Takashima H, Sato-Watanabe M, Chonan S, Yamamoto K, Saitoh M, Saito S, Yoshimura H, Sugawara K, Yang J, et al. Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1. FEBS Lett. 2004;566(1–3):55–9.PubMedCrossRef Murakami S, Takashima H, Sato-Watanabe M, Chonan S, Yamamoto K, Saitoh M, Saito S, Yoshimura H, Sugawara K, Yang J, et al. Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1. FEBS Lett. 2004;566(1–3):55–9.PubMedCrossRef
48.
go back to reference Yu R, Chen JA, Xu J, Cao J, Wang Y, Thomas SS, Hu Z. Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney disease. J Cachexia Sarcopenia Muscle. 2017;8(2):327–41.PubMedCrossRef Yu R, Chen JA, Xu J, Cao J, Wang Y, Thomas SS, Hu Z. Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney disease. J Cachexia Sarcopenia Muscle. 2017;8(2):327–41.PubMedCrossRef
49.
go back to reference Chen Y, Hanaoka M, Chen P, Droma Y, Voelkel NF, Kubo K. Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema. American journal of physiology Lung cellular and molecular physiology. 2009;296(4):L648–56.PubMedCrossRef Chen Y, Hanaoka M, Chen P, Droma Y, Voelkel NF, Kubo K. Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema. American journal of physiology Lung cellular and molecular physiology. 2009;296(4):L648–56.PubMedCrossRef
50.
go back to reference Li Y, Li J, Li W, Li S, Tian Y, Lu X, Jiang S, Wang Y. Long-term effects of three Tiao-Bu Fei-Shen therapies on NF-κB/TGF-β1/smad2 signaling in rats with chronic obstructive pulmonary disease. BMC Complement Altern Med. 2014;14:140.PubMedPubMedCentralCrossRef Li Y, Li J, Li W, Li S, Tian Y, Lu X, Jiang S, Wang Y. Long-term effects of three Tiao-Bu Fei-Shen therapies on NF-κB/TGF-β1/smad2 signaling in rats with chronic obstructive pulmonary disease. BMC Complement Altern Med. 2014;14:140.PubMedPubMedCentralCrossRef
51.
go back to reference Leppäranta O, Myllärniemi M, Salmenkivi K, Kinnula V, Keski-Oja J, Koli K. Reduced phosphorylation of the TGF-Beta signal transducer Smad2 in emphysematous human lung. COPD. 2009;6(4):234–41.PubMedCrossRef Leppäranta O, Myllärniemi M, Salmenkivi K, Kinnula V, Keski-Oja J, Koli K. Reduced phosphorylation of the TGF-Beta signal transducer Smad2 in emphysematous human lung. COPD. 2009;6(4):234–41.PubMedCrossRef
52.
go back to reference Shin H, Ryu E, Oh E, Kang D. Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells. Lab Investig. 2015;95(10):1157–73.PubMedCrossRef Shin H, Ryu E, Oh E, Kang D. Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells. Lab Investig. 2015;95(10):1157–73.PubMedCrossRef
53.
go back to reference Shah P, Dupre T, Siskind L, Beverly L. Common cytotoxic chemotherapeutics induce epithelial-mesenchymal transition (EMT) downstream of ER stress. Oncotarget. 2017;8(14):22625–39.PubMedPubMedCentralCrossRef Shah P, Dupre T, Siskind L, Beverly L. Common cytotoxic chemotherapeutics induce epithelial-mesenchymal transition (EMT) downstream of ER stress. Oncotarget. 2017;8(14):22625–39.PubMedPubMedCentralCrossRef
54.
go back to reference Tang X, Liang X, Li M, Guo T, Duan N, Wang Y, Rong G, Yang L, Zhang S, Zhang J. ATF6 pathway of unfolded protein response mediates advanced oxidation protein product-induced hypertrophy and epithelial-to-mesenchymal transition in HK-2 cells. Mol Cell Biochem. 2015;407(1–2):197–207.PubMedCrossRef Tang X, Liang X, Li M, Guo T, Duan N, Wang Y, Rong G, Yang L, Zhang S, Zhang J. ATF6 pathway of unfolded protein response mediates advanced oxidation protein product-induced hypertrophy and epithelial-to-mesenchymal transition in HK-2 cells. Mol Cell Biochem. 2015;407(1–2):197–207.PubMedCrossRef
55.
go back to reference Tanjore H, Cheng D, Degryse A, Zoz D, Abdolrasulnia R, Lawson W, Blackwell T. Alveolar epithelial cells undergo epithelial-to-mesenchymal transition in response to endoplasmic reticulum stress. J Biol Chem. 2015;290(6):3277.PubMedPubMedCentralCrossRef Tanjore H, Cheng D, Degryse A, Zoz D, Abdolrasulnia R, Lawson W, Blackwell T. Alveolar epithelial cells undergo epithelial-to-mesenchymal transition in response to endoplasmic reticulum stress. J Biol Chem. 2015;290(6):3277.PubMedPubMedCentralCrossRef
56.
go back to reference Liang X, Duan N, Wang Y, Shu S, Xiang X, Guo T, Yang L, Zhang S, Tang X, Zhang J. Advanced oxidation protein products induce endothelial-to-mesenchymal transition in human renal glomerular endothelial cells through induction of endoplasmic reticulum stress. J Diabetes Complicat. 2016;30(4):573–9.CrossRef Liang X, Duan N, Wang Y, Shu S, Xiang X, Guo T, Yang L, Zhang S, Tang X, Zhang J. Advanced oxidation protein products induce endothelial-to-mesenchymal transition in human renal glomerular endothelial cells through induction of endoplasmic reticulum stress. J Diabetes Complicat. 2016;30(4):573–9.CrossRef
57.
go back to reference Ying R, Wang X, Yang Y, Gu Z, Mai J, Qiu Q, Chen Y, Wang J. Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway. Life Sci. 2016;144:208–17.PubMedCrossRef Ying R, Wang X, Yang Y, Gu Z, Mai J, Qiu Q, Chen Y, Wang J. Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway. Life Sci. 2016;144:208–17.PubMedCrossRef
Metadata
Title
Ursolic acid alleviates airway-vessel remodeling and muscle consumption in cigarette smoke-induced emphysema rats
Authors
Li Lin
Gang Hou
Dan Han
Yan Yin
Jian Kang
Qiuyue Wang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2019
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-019-0826-6

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