Skip to main content
Top
Published in: Respiratory Research 1/2014

Open Access 01-12-2014 | Research

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat

Authors: Xue-Feng Xu, Qiong-Yao Hu, Ling-Fang Liang, Lei Wu, Wei-Zhong Gu, Li-Li Tang, Lin-Chen Fu, Li-Zhong Du

Published in: Respiratory Research | Issue 1/2014

Login to get access

Abstract

Background

Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.

Methods

An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.

Results

Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.

Conclusions

These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.
Appendix
Available only for authorised users
Literature
1.
go back to reference Xu XF, Du LZ: Epigenetics in neonatal diseases. Chin Med J (Engl). 2010, 123: 2948-2954. Xu XF, Du LZ: Epigenetics in neonatal diseases. Chin Med J (Engl). 2010, 123: 2948-2954.
2.
go back to reference Barker DJP: Fetal and infant origins of adult disease. Monatsschr Kinderheilkd. 2001, 149: S2-S6. 10.1007/s001120170002.CrossRef Barker DJP: Fetal and infant origins of adult disease. Monatsschr Kinderheilkd. 2001, 149: S2-S6. 10.1007/s001120170002.CrossRef
3.
go back to reference Anand D, Stevenson CJ, West CR, Pharoah POD: Lung function and respiratory health in adolescents of very low birth weight. Arch Dis Child. 2003, 88: 135-138. 10.1136/adc.88.2.135.PubMedPubMedCentralCrossRef Anand D, Stevenson CJ, West CR, Pharoah POD: Lung function and respiratory health in adolescents of very low birth weight. Arch Dis Child. 2003, 88: 135-138. 10.1136/adc.88.2.135.PubMedPubMedCentralCrossRef
4.
go back to reference Dezateux C, Lum S, Hoo AF, Hawdon J, Costeloe K, Stocks J: Low birth weight for gestation and airway function in infancy: exploring the fetal origins hypothesis. Thorax. 2004, 59: 60-66.PubMedPubMedCentral Dezateux C, Lum S, Hoo AF, Hawdon J, Costeloe K, Stocks J: Low birth weight for gestation and airway function in infancy: exploring the fetal origins hypothesis. Thorax. 2004, 59: 60-66.PubMedPubMedCentral
5.
go back to reference Morsing E, Gustafsson P, Brodszki J: Lung function in children born after foetal growth restriction and very preterm birth. Acta Paediatr. 2012, 101: 48-54. 10.1111/j.1651-2227.2011.02435.x.PubMedCrossRef Morsing E, Gustafsson P, Brodszki J: Lung function in children born after foetal growth restriction and very preterm birth. Acta Paediatr. 2012, 101: 48-54. 10.1111/j.1651-2227.2011.02435.x.PubMedCrossRef
6.
go back to reference Hack M, Taylor HG, Drotar D, Schluchter M, Cartar L, Andreias L, Wilson-Costello D, Klein N: Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s. JAMA. 2005, 294: 318-325. 10.1001/jama.294.3.318.PubMedCrossRef Hack M, Taylor HG, Drotar D, Schluchter M, Cartar L, Andreias L, Wilson-Costello D, Klein N: Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s. JAMA. 2005, 294: 318-325. 10.1001/jama.294.3.318.PubMedCrossRef
7.
go back to reference Seidman DS, Laor A, Gale R, Stevenson DK, Danon YL: Is Low-Birth-Weight a Risk Factor for Asthma during Adolescence. Arch Dis Child. 1991, 66: 584-587. 10.1136/adc.66.5.584.PubMedPubMedCentralCrossRef Seidman DS, Laor A, Gale R, Stevenson DK, Danon YL: Is Low-Birth-Weight a Risk Factor for Asthma during Adolescence. Arch Dis Child. 1991, 66: 584-587. 10.1136/adc.66.5.584.PubMedPubMedCentralCrossRef
8.
go back to reference Shaheen SO, Sterne JAC, Montgomery SM, Azima H: Birth weight, body mass index and asthma in young adults. Thorax. 1999, 54: 396-402. 10.1136/thx.54.5.396.PubMedPubMedCentralCrossRef Shaheen SO, Sterne JAC, Montgomery SM, Azima H: Birth weight, body mass index and asthma in young adults. Thorax. 1999, 54: 396-402. 10.1136/thx.54.5.396.PubMedPubMedCentralCrossRef
9.
go back to reference Lu FL, Hsieh CJ, Caffrey JL, Lin MH, Lin YS, Lin CC, Tsai MS, Ho WC, Chen PC, Sung FC, Lin RS: Body mass index may modify asthma prevalence among low-birth-weight children. Am J Epidemiol. 2012, 176: 32-42. 10.1093/aje/kwr484.PubMedCrossRef Lu FL, Hsieh CJ, Caffrey JL, Lin MH, Lin YS, Lin CC, Tsai MS, Ho WC, Chen PC, Sung FC, Lin RS: Body mass index may modify asthma prevalence among low-birth-weight children. Am J Epidemiol. 2012, 176: 32-42. 10.1093/aje/kwr484.PubMedCrossRef
10.
go back to reference Doyle LW: Respiratory function at age 8-9 years in extremely low birthweight/very preterm children born in Victoria in 1991-1992. Pediatr Pulmonol. 2006, 41: 570-576. 10.1002/ppul.20412.PubMedCrossRef Doyle LW: Respiratory function at age 8-9 years in extremely low birthweight/very preterm children born in Victoria in 1991-1992. Pediatr Pulmonol. 2006, 41: 570-576. 10.1002/ppul.20412.PubMedCrossRef
11.
go back to reference Sonnenschein-van der Voort AM, Arends LR, de Jongste JC, Annesi-Maesano I, Arshad SH, Barros H, Basterrechea M, Bisgaard H, Chatzi L, Corpeleijn E, Correia S, Craig LC, Devereux G, Dogaru C, Dostal M, Duchen K, Eggesbo M, van der Ent CK, Fantini MP, Forastiere F, Frey U, Gehring U, Gori D, van der Gugten AC, Hanke W, Henderson AJ, Heude B, Iniguez C, Inskip HM, Keil T, et al: Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children. J Allergy Clin Immunol. 2014, 133: 1317-1329. 10.1016/j.jaci.2013.12.1082.PubMedPubMedCentralCrossRef Sonnenschein-van der Voort AM, Arends LR, de Jongste JC, Annesi-Maesano I, Arshad SH, Barros H, Basterrechea M, Bisgaard H, Chatzi L, Corpeleijn E, Correia S, Craig LC, Devereux G, Dogaru C, Dostal M, Duchen K, Eggesbo M, van der Ent CK, Fantini MP, Forastiere F, Frey U, Gehring U, Gori D, van der Gugten AC, Hanke W, Henderson AJ, Heude B, Iniguez C, Inskip HM, Keil T, et al: Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children. J Allergy Clin Immunol. 2014, 133: 1317-1329. 10.1016/j.jaci.2013.12.1082.PubMedPubMedCentralCrossRef
12.
go back to reference Villamor E, Iliadou A, Cnattingius S: Is the association between low birth weight and asthma independent of genetic and shared environmental factors?. Am J Epidemiol. 2009, 169: 1337-1343. 10.1093/aje/kwp054.PubMedCrossRef Villamor E, Iliadou A, Cnattingius S: Is the association between low birth weight and asthma independent of genetic and shared environmental factors?. Am J Epidemiol. 2009, 169: 1337-1343. 10.1093/aje/kwp054.PubMedCrossRef
13.
go back to reference Joss-Moore LA, Albertine KH, Lane RH: Epigenetics and the developmental origins of lung disease. Mol Genet Metab. 2011, 104: 61-66. 10.1016/j.ymgme.2011.07.018.PubMedPubMedCentralCrossRef Joss-Moore LA, Albertine KH, Lane RH: Epigenetics and the developmental origins of lung disease. Mol Genet Metab. 2011, 104: 61-66. 10.1016/j.ymgme.2011.07.018.PubMedPubMedCentralCrossRef
14.
go back to reference Park JH, Stoffers DA, Nicholls RD, Simmons RA: Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Investig. 2008, 118: 2316-2324.PubMedPubMedCentralCrossRef Park JH, Stoffers DA, Nicholls RD, Simmons RA: Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Investig. 2008, 118: 2316-2324.PubMedPubMedCentralCrossRef
15.
go back to reference Pham TD, MacLennan NK, Chiu CT, Laksana GS, Hsu JL, Lane RH: Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol. 2003, 285: R962-R970.PubMedCrossRef Pham TD, MacLennan NK, Chiu CT, Laksana GS, Hsu JL, Lane RH: Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol. 2003, 285: R962-R970.PubMedCrossRef
16.
go back to reference Raychaudhuri N, Raychaudhuri S, Thamotharan M, Devaskar SU: Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J Biol Chem. 2008, 283: 13611-13626. 10.1074/jbc.M800128200.PubMedPubMedCentralCrossRef Raychaudhuri N, Raychaudhuri S, Thamotharan M, Devaskar SU: Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J Biol Chem. 2008, 283: 13611-13626. 10.1074/jbc.M800128200.PubMedPubMedCentralCrossRef
17.
go back to reference Simmons RA: Developmental origins of beta-cell failure in type 2 diabetes: The role of epigenetic mechanisms. Pediatr Res. 2007, 61: 64r-67r. 10.1203/pdr.0b013e3180457623.PubMedCrossRef Simmons RA: Developmental origins of beta-cell failure in type 2 diabetes: The role of epigenetic mechanisms. Pediatr Res. 2007, 61: 64r-67r. 10.1203/pdr.0b013e3180457623.PubMedCrossRef
18.
go back to reference Xu XF, Lv Y, Gu WZ, Tang LL, Wei JK, Zhang LY, Du LZ: Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR. Respir Res. 2013, 14: 20-10.1186/1465-9921-14-20.PubMedPubMedCentralCrossRef Xu XF, Lv Y, Gu WZ, Tang LL, Wei JK, Zhang LY, Du LZ: Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR. Respir Res. 2013, 14: 20-10.1186/1465-9921-14-20.PubMedPubMedCentralCrossRef
19.
go back to reference Chen PY, Ganguly A, Rubbi L, Orozco LD, Morselli M, Ashraf D, Jaroszewicz A, Feng S, Jacobsen SE, Nakano A, Devaskar SU, Pellegrini M: Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genomics. 2013, 45: 565-576. 10.1152/physiolgenomics.00034.2013.PubMedPubMedCentralCrossRef Chen PY, Ganguly A, Rubbi L, Orozco LD, Morselli M, Ashraf D, Jaroszewicz A, Feng S, Jacobsen SE, Nakano A, Devaskar SU, Pellegrini M: Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiol Genomics. 2013, 45: 565-576. 10.1152/physiolgenomics.00034.2013.PubMedPubMedCentralCrossRef
20.
go back to reference Lv Y, Tang LL, Wei JK, Xu XF, Gu W, Fu LC, Zhang LY, Du LZ: Decreased Kv1.5 expression in intrauterine growth retardation rats with exaggerated pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2013, 305: L856-L865. 10.1152/ajplung.00179.2013.PubMedCrossRef Lv Y, Tang LL, Wei JK, Xu XF, Gu W, Fu LC, Zhang LY, Du LZ: Decreased Kv1.5 expression in intrauterine growth retardation rats with exaggerated pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2013, 305: L856-L865. 10.1152/ajplung.00179.2013.PubMedCrossRef
21.
go back to reference Chalmers GW, Little SA, Patel KR, Thomson NC: Endothelin-1-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1997, 156: 382-388. 10.1164/ajrccm.156.2.9702066.PubMedCrossRef Chalmers GW, Little SA, Patel KR, Thomson NC: Endothelin-1-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1997, 156: 382-388. 10.1164/ajrccm.156.2.9702066.PubMedCrossRef
23.
go back to reference Trakada G, Tsourapis S, Marangos M, Spiropoulos K: Arterial and bronchoalveolar lavage fluid endothelin-1 concentration in asthma. Respir Med. 2000, 94: 992-996. 10.1053/rmed.2000.0890.PubMedCrossRef Trakada G, Tsourapis S, Marangos M, Spiropoulos K: Arterial and bronchoalveolar lavage fluid endothelin-1 concentration in asthma. Respir Med. 2000, 94: 992-996. 10.1053/rmed.2000.0890.PubMedCrossRef
24.
go back to reference Pegorier S, Arouche N, Dombret MC, Aubier M, Pretolani M: Augmented epithelial endothelin-1 expression in refractory asthma. J Allergy Clin Immunol. 2007, 120: 1301-1307. 10.1016/j.jaci.2007.09.023.PubMedCrossRef Pegorier S, Arouche N, Dombret MC, Aubier M, Pretolani M: Augmented epithelial endothelin-1 expression in refractory asthma. J Allergy Clin Immunol. 2007, 120: 1301-1307. 10.1016/j.jaci.2007.09.023.PubMedCrossRef
25.
go back to reference Salmon M, Liu YC, Mak JCW, Rousell J, Huang TJ, Hisada T, Nicklin PL, Chung KF: Contribution of upregulated airway endothelin-1 expression to airway smooth muscle and epithelial cell DNA synthesis after repeated allergen exposure of sensitized Brown-Norway rats. Am J Respir Cell Mol Biol. 2000, 23: 618-625. 10.1165/ajrcmb.23.5.3909.PubMedCrossRef Salmon M, Liu YC, Mak JCW, Rousell J, Huang TJ, Hisada T, Nicklin PL, Chung KF: Contribution of upregulated airway endothelin-1 expression to airway smooth muscle and epithelial cell DNA synthesis after repeated allergen exposure of sensitized Brown-Norway rats. Am J Respir Cell Mol Biol. 2000, 23: 618-625. 10.1165/ajrcmb.23.5.3909.PubMedCrossRef
26.
go back to reference McWhinnie R, Pechkovsky DV, Zhou D, Lane D, Halayko AJ, Knight DA, Bai TR: Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2007, 292: L278-L286. 10.1152/ajplung.00111.2006.PubMedCrossRef McWhinnie R, Pechkovsky DV, Zhou D, Lane D, Halayko AJ, Knight DA, Bai TR: Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2007, 292: L278-L286. 10.1152/ajplung.00111.2006.PubMedCrossRef
27.
go back to reference Koga H, Miyahara N, Fuchimoto Y, Ikeda G, Waseda K, Ono K, Tanimoto Y, Kataoka M, Gelfand EW, Tanimoto M, Kanehiro A: Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses. Respir Res. 2013, 14: 8-10.1186/1465-9921-14-8.PubMedPubMedCentralCrossRef Koga H, Miyahara N, Fuchimoto Y, Ikeda G, Waseda K, Ono K, Tanimoto Y, Kataoka M, Gelfand EW, Tanimoto M, Kanehiro A: Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses. Respir Res. 2013, 14: 8-10.1186/1465-9921-14-8.PubMedPubMedCentralCrossRef
28.
go back to reference Xu XF, Ma XL, Shen Z, Wu XL, Cheng F, Du LZ: Epigenetic regulation of the endothelial nitric oxide synthase gene in persistent pulmonary hypertension of the newborn rat. J Hypertens. 2010, 28: 2227-2235. 10.1097/HJH.0b013e32833e08f1.PubMedCrossRef Xu XF, Ma XL, Shen Z, Wu XL, Cheng F, Du LZ: Epigenetic regulation of the endothelial nitric oxide synthase gene in persistent pulmonary hypertension of the newborn rat. J Hypertens. 2010, 28: 2227-2235. 10.1097/HJH.0b013e32833e08f1.PubMedCrossRef
29.
go back to reference Xu XF, Gu WZ, Wu XL, Li RY, Du LZ: Fetal pulmonary vascular remodeling in a rat model induced by hypoxia and indomethacin. J Matern Fetal Neonatal Med. 2011, 24: 172-182. 10.3109/14767058.2010.482608.PubMedCrossRef Xu XF, Gu WZ, Wu XL, Li RY, Du LZ: Fetal pulmonary vascular remodeling in a rat model induced by hypoxia and indomethacin. J Matern Fetal Neonatal Med. 2011, 24: 172-182. 10.3109/14767058.2010.482608.PubMedCrossRef
30.
go back to reference Hsia CC, Hyde DM, Ochs M, Weibel ER: An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010, 181: 394-418. 10.1164/rccm.200809-1522ST.PubMedCrossRef Hsia CC, Hyde DM, Ochs M, Weibel ER: An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010, 181: 394-418. 10.1164/rccm.200809-1522ST.PubMedCrossRef
32.
go back to reference Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li ZW, Tomfohr J, Bailey N, Potts EN, Whitehead G, Brass DM, Schwartz DA: In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Investig. 2008, 118: 3462-3469.PubMedPubMedCentral Hollingsworth JW, Maruoka S, Boon K, Garantziotis S, Li ZW, Tomfohr J, Bailey N, Potts EN, Whitehead G, Brass DM, Schwartz DA: In utero supplementation with methyl donors enhances allergic airway disease in mice. J Clin Investig. 2008, 118: 3462-3469.PubMedPubMedCentral
33.
go back to reference Tang WY, Levin L, Talaska G, Cheung YY, Herbstman J, Tang D, Miller RL, Perera F, Ho SM: Maternal exposure to polycyclic aromatic hydrocarbons and 5'-CpG methylation of interferon-gamma in cord white blood cells. Environ Health Perspect. 2012, 120: 1195-1200. 10.1289/ehp.1103744.PubMedPubMedCentralCrossRef Tang WY, Levin L, Talaska G, Cheung YY, Herbstman J, Tang D, Miller RL, Perera F, Ho SM: Maternal exposure to polycyclic aromatic hydrocarbons and 5'-CpG methylation of interferon-gamma in cord white blood cells. Environ Health Perspect. 2012, 120: 1195-1200. 10.1289/ehp.1103744.PubMedPubMedCentralCrossRef
34.
go back to reference Gregory LG, Jones CP, Mathie SA, Pegorier S, Lloyd CM: Endothelin-1 directs airway remodeling and hyper-reactivity in a murine asthma model. Allergy. 2013, 68: 1579-1588. 10.1111/all.12271.PubMedPubMedCentralCrossRef Gregory LG, Jones CP, Mathie SA, Pegorier S, Lloyd CM: Endothelin-1 directs airway remodeling and hyper-reactivity in a murine asthma model. Allergy. 2013, 68: 1579-1588. 10.1111/all.12271.PubMedPubMedCentralCrossRef
35.
go back to reference Zietkowski Z, Skiepko R, Tomasiak MM, Bodzenta-Lukaszyk A: Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction. Respir Res. 2007, 8: 76-10.1186/1465-9921-8-76.PubMedPubMedCentralCrossRef Zietkowski Z, Skiepko R, Tomasiak MM, Bodzenta-Lukaszyk A: Endothelin-1 in exhaled breath condensate of allergic asthma patients with exercise-induced bronchoconstriction. Respir Res. 2007, 8: 76-10.1186/1465-9921-8-76.PubMedPubMedCentralCrossRef
36.
go back to reference Hu J, Discher DJ, Bishopric NH, Webster KA: Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand. Biochem Biophys Res Commun. 1998, 245: 894-899. 10.1006/bbrc.1998.8543.PubMedCrossRef Hu J, Discher DJ, Bishopric NH, Webster KA: Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand. Biochem Biophys Res Commun. 1998, 245: 894-899. 10.1006/bbrc.1998.8543.PubMedCrossRef
37.
go back to reference Teplyakov AI: Epigenetic topography of lymphocyte nuclei and endothelin-1 at atherosclerosis. J Cardiovasc Pharmacol. 2004, 44 (Suppl 1): S490-S491. 10.1097/01.fjc.0000166306.79055.76.PubMedCrossRef Teplyakov AI: Epigenetic topography of lymphocyte nuclei and endothelin-1 at atherosclerosis. J Cardiovasc Pharmacol. 2004, 44 (Suppl 1): S490-S491. 10.1097/01.fjc.0000166306.79055.76.PubMedCrossRef
38.
go back to reference Yamashita K, Discher DJ, Hu J, Bishopric NH, Webster KA: Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP. J Biol Chem. 2001, 276: 12645-12653. 10.1074/jbc.M011344200.PubMedCrossRef Yamashita K, Discher DJ, Hu J, Bishopric NH, Webster KA: Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP. J Biol Chem. 2001, 276: 12645-12653. 10.1074/jbc.M011344200.PubMedCrossRef
Metadata
Title
Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat
Authors
Xue-Feng Xu
Qiong-Yao Hu
Ling-Fang Liang
Lei Wu
Wei-Zhong Gu
Li-Li Tang
Lin-Chen Fu
Li-Zhong Du
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2014
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-014-0137-7

Other articles of this Issue 1/2014

Respiratory Research 1/2014 Go to the issue