Top

Published in:

Open Access 01-12-2023 | Bronchial Asthma | Research

Macrophage migration inhibitory factor exacerbates asthmatic airway remodeling via dynamin-related protein 1-mediated autophagy activation

Authors: Jin Liu, Yuqian Chen, Huan Chen, Yan Wang, Danyang Li, Qianqian Zhang, Limin Chai, Yuanjie Qiu, Jia Zhang, Nirui Shen, Qingting Wang, Jian Wang, Manxiang Li

Published in: Respiratory Research | Issue 1/2023

Abstract

Background

Macrophage migration inhibitory factor (MIF) and GTPase dynamin-related protein 1 (Drp1)-dependent aberrant mitochondrial fission are closely linked to the pathogenesis of asthma. However, it is unclear whether Drp1-mediated mitochondrial fission and its downstream targets mediate MIF-induced proliferation of airway smooth muscle cells (ASMCs) in vitro and airway remodeling in chronic asthma models. The present study aims to clarify these issues.

Methods

In this study, primary cultured ASMCs and ovalbumin (OVA)-induced asthmatic rats were applied. Cell proliferation was detected by CCK-8 and EdU assays. Western blotting was used to detect extracellular signal-regulated kinase (ERK) 1/2, Drp1, autophagy-related markers and E-cadherin protein phosphorylation and expression. Inflammatory cytokines production, airway reactivity test, histological staining and immunohistochemical staining were conducted to evaluate the development of asthma. Transmission electron microscopy was used to observe the mitochondrial ultrastructure.

Results

In primary cultured ASMCs, MIF increased the phosphorylation level of Drp1 at the Ser616 site through activation of the ERK1/2 signaling pathway, which further activated autophagy and reduced E-cadherin expression, ultimately leading to ASMCs proliferation. In OVA-induced asthmatic rats, MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) treatment, suppression of mitochondrial fission by Mdivi-1 or inhibiting autophagy with chloroquine phosphate (CQ) all attenuated the development of airway remodeling.

Conclusions

The present study provides novel insights that MIF promotes airway remodeling in asthma by activating autophagy and degradation of E-cadherin via ERK/Drp1 signaling pathway, suggesting that targeting MIF/ERK/Drp1 might have potential therapeutic value for the prevention and treatment of asthma.

Available only for authorised users

Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018;391:783–800.PubMed

Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16:45–56.PubMed

Camoretti-Mercado B, Lockey RF. Airway smooth muscle pathophysiology in asthma. J Allergy Clin Immunol. 2021;147:1983–95.PubMed

Kang I, Bucala R. The immunobiology of MIF: function, genetics and prospects for precision medicine. Nat Rev Rheumatol. 2019;15:427–37.PubMed

Florez-Sampedro L, Soto-Gamez A, Poelarends GJ, Melgert BN. The role of MIF in chronic lung diseases: looking beyond inflammation. Am J Physiol Lung Cell Mol Physiol. 2020;318:L1183-l1197.PubMed

Li R, Wang F, Wei J, Lin Y, Tang G, Rao L, Ma L, Xu Q, Wu J, Lv Q, et al. The role of macrophage migration inhibitory factor (MIF) in asthmatic airway remodeling. Allergy Asthma Immunol Res. 2021;13:88–105.PubMed

Lintomen L, Kluppel LM, Kitoko JZ, Montes-Cobos E, Vidal VM, Tan LB, de Farias JN, de Souza HS, Olsen PC, Bozza MT. MIF is essential to the establishment of house dust mite-induced airway inflammation and tissue remodeling in mice. Eur J Immunol. 2023:e2250016.

Kobayashi M, Nasuhara Y, Kamachi A, Tanino Y, Betsuyaku T, Yamaguchi E, Nishihira J, Nishimura M. Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats. Eur Respir J. 2006;27:726–34.PubMed

Zheng L, Gao J, Jin K, Chen Z, Yu W, Zhu K, Huang W, Liu F, Mei L, Lou C, He D. Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF-κB signaling pathway. Faseb j. 2019;33:7667–83.PubMed

10.

Winner M, Meier J, Zierow S, Rendon BE, Crichlow GV, Riggs R, Bucala R, Leng L, Smith N, Lolis E, et al. A novel, macrophage migration inhibitory factor suicide substrate inhibits motility and growth of lung cancer cells. Cancer Res. 2008;68:7253–7.PubMedPubMedCentral

11.

Sun W, Ma J, Chen M, Zhang W, Xu C, Nan Y, Wu W, Mao X, Cheng X, Cai H, et al. 4-Iodo-6-phenylpyrimidine (4-IPP) suppresses fibroblast-like synoviocyte- mediated inflammation and joint destruction associated with rheumatoid arthritis. Int Immunopharmacol. 2023;115: 109714.PubMed

12.

Zhang L, Ma C, Wang X, He S, Li Q, Zhou Y, Liu Y, Zhang M, Yu X, Zhao X, et al. Lipopolysaccharide-induced proliferation and glycolysis in airway smooth muscle cells via activation of Drp1. J Cell Physiol. 2019;234:9255–63.PubMed

13.

Bruno SR, Kumar A, Mark ZF, Chandrasekaran R, Nakada E, Chamberlain N, Mihavics B, Walzer J, Cahoon J, Dixon AE, et al. DRP1-mediated mitochondrial fission regulates lung epithelial response to allergen. Int J Mol Sci. 2021; 22.

14.

Delmotte P, Marin Mathieu N, Sieck GC. TNFα induces mitochondrial fragmentation and biogenesis in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2021;320:L137-l151.PubMed

15.

Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science. 2012;337:1062–5.PubMedPubMedCentral

16.

Sharma A, Ahmad S, Ahmad T, Ali S, Syed MA. Mitochondrial dynamics and mitophagy in lung disorders. Life Sci. 2021;284: 119876.PubMed

17.

Xu T, Dong Q, Luo Y, Liu Y, Gao L, Pan Y, Zhang D. Porphyromonas gingivalis infection promotes mitochondrial dysfunction through Drp1-dependent mitochondrial fission in endothelial cells. Int J Oral Sci. 2021;13:28.PubMedPubMedCentral

18.

Feng W, Wang J, Yan X, Zhang Q, Chai L, Wang Q, Shi W, Chen Y, Liu J, Qu Z, et al. ERK/Drp1-dependent mitochondrial fission contributes to HMGB1-induced autophagy in pulmonary arterial hypertension. Cell Prolif. 2021;54: e13048.PubMedPubMedCentral

19.

Xiong X, Hasani S, Young LEA, Rivas DR, Skaggs AT, Martinez R, Wang C, Weiss HL, Gentry MS, Sun RC, Gao T. Activation of Drp1 promotes fatty acids-induced metabolic reprograming to potentiate Wnt signaling in colon cancer. Cell Death Differ. 2022;29:1913–27.PubMedPubMedCentral

20.

Chen P, Lu Y, He B, Xie T, Yan C, Liu T, Wu S, Yeh Y, Li Z, Huang W, Zhang X. Rab32 promotes glioblastoma migration and invasion via regulation of ERK/Drp1-mediated mitochondrial fission. Cell Death Dis. 2023;14:198.PubMedPubMedCentral

21.

Nawijn MC, Hackett TL, Postma DS, van Oosterhout AJ, Heijink IH. E-cadherin: gatekeeper of airway mucosa and allergic sensitization. Trends Immunol. 2011;32:248–55.PubMed

22.

Bedel A, Nègre-Salvayre A, Heeneman S, Grazide MH, Thiers JC, Salvayre R, Maupas-Schwalm F. E-cadherin/beta-catenin/T-cell factor pathway is involved in smooth muscle cell proliferation elicited by oxidized low-density lipoprotein. Circ Res. 2008;103:694–701.PubMed

23.

Zhai C, Feng W, Shi W, Wang J, Zhang Q, Yan X, Wang Q, Li S, Liu L, Pan Y, et al. Sphingosine-1-phosphate promotes pulmonary artery smooth muscle cells proliferation by stimulating autophagy-mediated E-cadherin/CDH1 down-regulation. Eur J Pharmacol. 2020;884: 173302.PubMed

24.

Funamizu N, Hu C, Lacy C, Schetter A, Zhang G, He P, Gaedcke J, Ghadimi MB, Ried T, Yfantis HG, et al. Macrophage migration inhibitory factor induces epithelial to mesenchymal transition, enhances tumor aggressiveness and predicts clinical outcome in resected pancreatic ductal adenocarcinoma. Int J Cancer. 2013;132:785–94.PubMedPubMedCentral

25.

Huang G, Ma L, Shen L, Lei Y, Guo L, Deng Y, Ding Y. MIF/SCL3A2 depletion inhibits the proliferation and metastasis of colorectal cancer cells via the AKT/GSK-3β pathway and cell iron death. J Cell Mol Med. 2022;26:3410–22.PubMedPubMedCentral

26.

Pan Y, Liu L, Li S, Wang K, Ke R, Shi W, Wang J, Yan X, Zhang Q, Wang Q, et al. Activation of AMPK inhibits TGF-β1-induced airway smooth muscle cells proliferation and its potential mechanisms. Sci Rep. 2018;8:3624.PubMedPubMedCentral

27.

Shi ZF, Fang Q, Chen Y, Xu LX, Wu M, Jia M, Lu Y, Wang XX, Wang YJ, Yan X, et al. Methylene blue ameliorates brain edema in rats with experimental ischemic stroke via inhibiting aquaporin 4 expression. Acta Pharmacol Sin. 2021;42:382–92.PubMed

28.

Lee SH, Kwon HJ, Park S, Kim CI, Ryu H, Kim SS, Park JB, Kwon JT. Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP downregulates stemness phenotype and mesenchymal trans-differentiation after irradiation in glioblastoma multiforme. PLoS ONE. 2021;16: e0257375.PubMedPubMedCentral

29.

Marsboom G, Toth PT, Ryan JJ, Hong Z, Wu X, Fang YH, Thenappan T, Piao L, Zhang HJ, Pogoriler J, et al. Dynamin-related protein 1-mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension. Circ Res. 2012;110:1484–97.PubMedPubMedCentral

30.

Wang Z, Wu Y, Pei C, Wang M, Wang X, Shi S, Huang D, Wang Y, Li S, Xiao W, et al. Astragaloside IV pre-treatment attenuates PM2.5-induced lung injury in rats: impact on autophagy, apoptosis and inflammation. Phytomedicine. 2022;96:153912.PubMed

31.

Liu Y, Li X, He C, Chen R, Wei L, Meng L, Zhang C. Emodin ameliorates ovalbumin-induced airway remodeling in mice by suppressing airway smooth muscle cells proliferation. Int Immunopharmacol. 2020;88: 106855.PubMed

32.

Zhang Q, Chen Y, Wang Q, Wang Y, Feng W, Chai L, Liu J, Li D, Chen H, Qiu Y, et al. HMGB1-induced activation of ER stress contributes to pulmonary artery hypertension in vitro and in vivo. Respir Res. 2023;24:149.PubMedPubMedCentral

33.

Huang Q, Zhan L, Cao H, Li J, Lyu Y, Guo X, Zhang J, Ji L, Ren T, An J, et al. Increased mitochondrial fission promotes autophagy and hepatocellular carcinoma cell survival through the ROS-modulated coordinated regulation of the NFKB and TP53 pathways. Autophagy. 2016;12:999–1014.PubMedPubMedCentral

34.

Wirtz TH, Saal A, Bergmann I, Fischer P, Heinrichs D, Brandt EF, Koenen MT, Djudjaj S, Schneider KM, Boor P, et al. Macrophage migration inhibitory factor exerts pro-proliferative and anti-apoptotic effects via CD74 in murine hepatocellular carcinoma. Br J Pharmacol. 2021;178:4452–67.PubMed

35.

Chen L, Zhou X, Fan LX, Yao Y, Swenson-Fields KI, Gadjeva M, Wallace DP, Peters DJ, Yu A, Grantham JJ, Li X. Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease. J Clin Invest. 2015;125:2399–412.PubMedPubMedCentral

36.

Al-Abed Y, Dabideen D, Aljabari B, Valster A, Messmer D, Ochani M, Tanovic M, Ochani K, Bacher M, Nicoletti F, et al. ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis. J Biol Chem. 2005;280:36541–4.PubMed

37.

Castro BA, Flanigan P, Jahangiri A, Hoffman D, Chen W, Kuang R, De Lay M, Yagnik G, Wagner JR, Mascharak S, et al. Macrophage migration inhibitory factor downregulation: a novel mechanism of resistance to anti-angiogenic therapy. Oncogene. 2017;36:3749–59.PubMedPubMedCentral

38.

Fukuda Y, Bustos MA, Cho SN, Roszik J, Ryu S, Lopez VM, Burks JK, Lee JE, Grimm EA, Hoon DSB, Ekmekcioglu S. Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma. Cell Death Dis. 2022;13:117.PubMedPubMedCentral

39.

Zhang Y, Zhu W, He H, Fan B, Deng R, Hong Y, Liang X, Zhao H, Li X, Zhang F. Macrophage migration inhibitory factor rejuvenates aged human mesenchymal stem cells and improves myocardial repair. Aging (Albany NY). 2019;11:12641–60.PubMed

40.

Allam V, Pavlidis S, Liu G, Kermani NZ, Simpson J, To J, Donnelly S, Guo YK, Hansbro PM, Phipps S, et al. Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma. Thorax. 2022;78:661.PubMed

41.

Jankauskas SS, Wong DWL, Bucala R, Djudjaj S, Boor P. Evolving complexity of MIF signaling. Cell Signal. 2019;57:76–88.PubMed

42.

He J, Zheng L, Li X, Huang F, Hu S, Chen L, Jiang M, Lin X, Jiang H, Zeng Y, et al. Obacunone targets macrophage migration inhibitory factor (MIF) to impede osteoclastogenesis and alleviate ovariectomy-induced bone loss. J Adv Res. 2023.

43.

Cui J, Zhang F, Wang Y, Liu J, Ming X, Hou J, Lv B, Fang S, Yu B. Macrophage migration inhibitory factor promotes cardiac stem cell proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK pathways. Int J Mol Med. 2016;37:1299–309.PubMedPubMedCentral

44.

Shi X, Leng L, Wang T, Wang W, Du X, Li J, McDonald C, Chen Z, Murphy JW, Lolis E, et al. CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity. 2006;25:595–606.PubMedPubMedCentral

45.

Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, Gemsa D, Donnelly T, Bucala R. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci U S A. 1996;93:7849–54.PubMedPubMedCentral

46.

Das R, Moss JE, Robinson E, Roberts S, Levy R, Mizue Y, Leng L, McDonald C, Tigelaar RE, Herrick CA, Bucala R. Role of macrophage migration inhibitory factor in the Th2 immune response to epicutaneous sensitization. J Clin Immunol. 2011;31:666–80.PubMedPubMedCentral

47.

Sun L, Tu J, Chen X, Dai M, Xia X, Liu C, Zhou Y. JNK pathway-associated phosphatase associates with rheumatoid arthritis risk, disease activity, and its longitudinal elevation relates to etanercept treatment response. J Clin Lab Anal. 2021;35: e23709.PubMedPubMedCentral

48.

Chen PF, Luo YL, Wang W, Wang JX, Lai WY, Hu SM, Cheng KF, Al-Abed Y. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma. Mol Med. 2010;16:400–8.PubMedPubMedCentral

49.

Lan H, Luo L, Chen Y, Wang M, Yu Z, Gong Y. MIF signaling blocking alleviates airway inflammation and airway epithelial barrier disruption in a HDM-induced asthma model. Cell Immunol. 2020;347: 103965.PubMed

50.

Rendon BE, Roger T, Teneng I, Zhao M, Al-Abed Y, Calandra T, Mitchell RA. Regulation of human lung adenocarcinoma cell migration and invasion by macrophage migration inhibitory factor. J Biol Chem. 2007;282:29910–8.PubMed

51.

Meyer-Siegler KL, Iczkowski KA, Leng L, Bucala R, Vera PL. Inhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU-145 prostate cancer cells. J Immunol. 2006;177:8730–9.PubMed

52.

Filbey KJ, Varyani F, Harcus Y, Hewitson JP, Smyth DJ, McSorley HJ, Ivens A, Nylén S, Rottenberg M, Löser S, Maizels RM. Macrophage migration inhibitory factor (MIF) is essential for Type 2 effector cell immunity to an intestinal helminth parasite. Front Immunol. 2019;10:2375.PubMedPubMedCentral

53.

Zhang Y, Liu Z, Wang K, Lu S, Fan S, Xu L, Cai B. Macrophage migration inhibitory factor regulates joint capsule fibrosis by promoting TGF-β1 production in fibroblasts. Int J Biol Sci. 2021;17:1837–50.PubMedPubMedCentral

54.

Ko HJ, Tsai CY, Chiou SJ, Lai YL, Wang CH, Cheng JT, Chuang TH, Huang CF, Kwan AL, Loh JK, Hong YR. The phosphorylation status of Drp1-Ser637 by PKA in mitochondrial fission modulates mitophagy via PINK1/Parkin to exert multipolar spindles assembly during mitosis. Biomolecules. 2021; 11.

55.

Zhang Y, Huang X, Sun T, Shi L, Liu B, Hong Y, Fu QL, Zhang Y, Li X. MicroRNA-19b-3p dysfunction of mesenchymal stem cell-derived exosomes from patients with abdominal aortic aneurysm impairs therapeutic efficacy. J Nanobiotechnology. 2023;21:135.PubMedPubMedCentral

56.

Wu F, Zhang YT, Teng F, Li HH, Guo SB. S100a8/a9 contributes to sepsis-induced cardiomyopathy by activating ERK1/2-Drp1-mediated mitochondrial fission and respiratory dysfunction. Int Immunopharmacol. 2023;115: 109716.PubMed

57.

Cha Y, Kim T, Jeon J, Jang Y, Kim PB, Lopes C, Leblanc P, Cohen BM, Kim KS. SIRT2 regulates mitochondrial dynamics and reprogramming via MEK1-ERK-DRP1 and AKT1-DRP1 axes. Cell Rep. 2021;37: 110155.PubMedPubMedCentral

58.

Martinet W, De Meyer GR. Autophagy in atherosclerosis: a cell survival and death phenomenon with therapeutic potential. Circ Res. 2009;104:304–17.PubMed

59.

Martinet W, De Meyer I, Verheye S, Schrijvers DM, Timmermans JP, De Meyer GR. Drug-induced macrophage autophagy in atherosclerosis: for better or worse? Basic Res Cardiol. 2013;108:321.PubMed

60.

Ban GY, Pham DL, Trinh TH, Lee SI, Suh DH, Yang EM, Ye YM, Shin YS, Chwae YJ, Park HS. Autophagy mechanisms in sputum and peripheral blood cells of patients with severe asthma: a new therapeutic target. Clin Exp Allergy. 2016;46:48–59.PubMed

61.

Liu JN, Suh DH, Trinh HK, Chwae YJ, Park HS, Shin YS. The role of autophagy in allergic inflammation: a new target for severe asthma. Exp Mol Med. 2016;48: e243.PubMedPubMedCentral

62.

Poon A, Eidelman D, Laprise C, Hamid Q. ATG5, autophagy and lung function in asthma. Autophagy. 2012;8:694–5.PubMed

63.

Liang Q, He J, Yang Q, Zhang Q, Xu Y. MicroRNA-335-5p alleviates inflammatory response, airway fibrosis, and autophagy in childhood asthma through targeted regulation of autophagy related 5. Bioengineered. 2022;13:1791–801.PubMedPubMedCentral

64.

Qu X, Sheng J, Shen L, Su J, Xu Y, Xie Q, Wu Y, Zhang X, Sun L. Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS. PLoS ONE. 2017;12: e0173712.PubMedPubMedCentral

65.

Schmidt RL, Jutz S, Goldhahn K, Witzeneder N, Gerner MC, Trapin D, Greiner G, Hoermann G, Steiner G, Pickl WF, et al. Chloroquine inhibits human CD4(+) T-cell activation by AP-1 signaling modulation. Sci Rep. 2017;7:42191.PubMedPubMedCentral

66.

Ren Y, Zhong X, Wang H, Chen Z, Liu Y, Zeng X, Ma Y. Chloroquine attenuates asthma development by restoring airway smooth muscle cell phenotype via the ROS-AKT pathway. Front Pharmacol. 2022;13: 916508.PubMedPubMedCentral

67.

van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008;65:3756–88.PubMed

68.

James AL, Wenzel S. Clinical relevance of airway remodelling in airway diseases. Eur Respir J. 2007;30:134–55.PubMed

69.

Dekkers BG, Maarsingh H, Meurs H, Gosens R. Airway structural components drive airway smooth muscle remodeling in asthma. Proc Am Thorac Soc. 2009;6:683–92.PubMed

70.

Davies DE. The role of the epithelium in airway remodeling in asthma. Proc Am Thorac Soc. 2009;6:678–82.PubMedPubMedCentral

71.

Ogawa H, Azuma M, Tsunematsu T, Morimoto Y, Kondo M, Tezuka T, Nishioka Y, Tsuneyama K. Neutrophils induce smooth muscle hyperplasia via neutrophil elastase-induced FGF-2 in a mouse model of asthma with mixed inflammation. Clin Exp Allergy. 2018;48:1715–25.PubMed

Title: Macrophage migration inhibitory factor exacerbates asthmatic airway remodeling via dynamin-related protein 1-mediated autophagy activation
Authors: Jin Liu
Yuqian Chen
Huan Chen
Yan Wang
Danyang Li
Qianqian Zhang
Limin Chai
Yuanjie Qiu
Jia Zhang
Nirui Shen
Qingting Wang
Jian Wang
Manxiang Li
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Bronchial Asthma
Published in: Respiratory Research / Issue 1/2023
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-023-02526-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

Trend and heterogeneity in forced vital capacity among Chinese students during 1985–2019: results from Chinese National Survey on Students’ Constitution and Health

RAGE inhibition alleviates lipopolysaccharides-induced lung injury via directly suppressing autophagic apoptosis of type II alveolar epithelial cells

An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma

Intense solar activity reduces urinary 6-sulfatoxymelatonin in patients with COPD

Evolution and long‑term respiratory sequelae after severe COVID-19 pneumonia: nitric oxide diffusion measurement value

Comparative cardiovascular safety of LABA/LAMA FDC versus LABA/ICS FDC in patients with chronic obstructive pulmonary disease: a population-based cohort study with a target trial emulation framework

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials