{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T19:53:23Z","timestamp":1777060403133,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Ministry for Education and Research","doi-asserted-by":"publisher","award":["82DZL004A1"],"award-info":[{"award-number":["82DZL004A1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Ministry for Education and Research","doi-asserted-by":"publisher","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Ministry for Education and Research","doi-asserted-by":"publisher","award":["450557679"],"award-info":[{"award-number":["450557679"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsche Forschungsgemeinschaft","award":["82DZL004A1"],"award-info":[{"award-number":["82DZL004A1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["450557679"],"award-info":[{"award-number":["450557679"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elevated levels of matrix metalloprotease 9 (MMP-9) and neutrophil elastase (NE) are associated with bronchiectasis and lung function decline in patients with cystic fibrosis (CF). MMP-9 is a potent extracellular matrix-degrading enzyme which is activated by NE and has been implicated in structural lung damage in CF. However, the role of MMP-9 in the in vivo pathogenesis of CF lung disease is not well understood. Therefore, we used \u03b2-epithelial Na+ channel-overexpressing transgenic (\u03b2ENaC-Tg) mice as a model of CF-like lung disease and determined the effect of genetic deletion of Mmp9 (Mmp9-\/-) on key aspects of the pulmonary phenotype. We found that MMP-9 levels were elevated in the lungs of \u03b2ENaC-Tg mice compared with wild-type littermates. Deletion of Mmp9 had no effect on spontaneous mortality, inflammatory markers in bronchoalveolar lavage, goblet cell metaplasia, mucus hypersecretion and emphysema-like structural lung damage, while it partially reduced mucus obstruction in \u03b2ENaC-Tg mice. Further, lack of Mmp9 had no effect on increased inspiratory capacity and increased lung compliance in \u03b2ENaC-Tg mice, whereas both lung function parameters were improved with genetic deletion of NE. We conclude that MMP-9 does not play a major role in the in vivo pathogenesis of CF-like lung disease in mice.<\/jats:p>","DOI":"10.3390\/ijms232113405","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T03:11:21Z","timestamp":1667445081000},"page":"13405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Deletion of Mmp9 Does Not Reduce Airway Inflammation and Structural Lung Damage in Mice with Cystic Fibrosis-like Lung Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Claudius","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Translational Pulmonology, University of Heidelberg, 69117 Heidelberg, Germany"},{"name":"Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-5239","authenticated-orcid":false,"given":"Anita","family":"Bal\u00e1zs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanthe","family":"Schatterny","sequence":"additional","affiliation":[{"name":"Department of Translational Pulmonology, University of Heidelberg, 69117 Heidelberg, Germany"},{"name":"Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Zhou-Suckow","sequence":"additional","affiliation":[{"name":"Department of Translational Pulmonology, University of Heidelberg, 69117 Heidelberg, Germany"},{"name":"Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4862-9487","authenticated-orcid":false,"given":"Julia","family":"Duerr","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Schultz","sequence":"additional","affiliation":[{"name":"Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany"},{"name":"Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2199","authenticated-orcid":false,"given":"Marcus A.","family":"Mall","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"German Center for Lung Research (DZL), Associated Partner Site, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic Fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1183\/09031936.00228013","article-title":"CFTR: Cystic Fibrosis and Beyond","volume":"44","author":"Mall","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1164\/rccm.201906-1190PP","article-title":"Targeting Proteases in Cystic Fibrosis Lung Disease. Paradigms, Progress, and Potential","volume":"201","author":"McKelvey","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1501200","DOI":"10.1183\/13993003.01200-2015","article-title":"Protean Proteases: At the Cutting Edge of Lung Diseases","volume":"49","author":"Taggart","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"McKelvey, M.C., Brown, R., Ryan, S., Mall, M.A., Weldon, S., and Taggart, C.C. (2021). Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22095018"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1164\/rccm.201803-0442OC","article-title":"Elastase Exocytosis by Airway Neutrophils Associates with Early Lung Damage in Cystic Fibrosis Children","volume":"199","author":"Margaroli","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1701910","DOI":"10.1183\/13993003.01910-2017","article-title":"Elastase Activity on Sputum Neutrophils Correlates with Severity of Lung Disease in Cystic Fibrosis","volume":"51","author":"Dittrich","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1080\/17476348.2016.1204915","article-title":"Diagnosis and Early Life Risk Factors for Bronchiectasis in Cystic Fibrosis: A Review","volume":"10","author":"Sly","year":"2016","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1164\/rccm.201311-1932OC","article-title":"Lack of Neutrophil Elastase Reduces Inflammation, Mucus Hypersecretion, and Emphysema, but Not Mucus Obstruction, in Mice with Cystic Fibrosis-like Lung Disease","volume":"189","author":"Gehrig","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26945","DOI":"10.1074\/jbc.M110.151803","article-title":"Airway Surface Liquid Volume Regulation Determines Different Airway Phenotypes in Liddle Compared with BetaENaC-Overexpressing Mice","volume":"285","author":"Mall","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Giacalone, V.D., Margaroli, C., Mall, M.A., and Tirouvanziam, R. (2020). Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030851"},{"key":"ref_12","first-page":"S5","article-title":"Mucus Obstruction and Inflammation in Early Cystic Fibrosis Lung Disease: Emerging Role of the IL-1 Signaling Pathway","volume":"54","author":"Mall","year":"2019","journal-title":"Pediatr. Pulmonol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1183\/09031936.00173210","article-title":"The Role of Matrix Metalloproteases in Cystic Fibrosis Lung Disease","volume":"38","author":"Gaggar","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1165\/rcmb.2002-0166TR","article-title":"Matrix Metalloproteinase-9 in Lung Remodeling","volume":"28","author":"Atkinson","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3389\/fphar.2017.00512","article-title":"Role of Proteases in Chronic Obstructive Pulmonary Disease","volume":"8","author":"Pandey","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.matbio.2015.01.016","article-title":"MMP Generated Matrikines","volume":"44\u201346","author":"Wells","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/path.1400","article-title":"Extracellular Matrix Remodelling: The Role of Matrix Metalloproteinases","volume":"200","author":"Stamenkovic","year":"2003","journal-title":"J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3109\/10409238.2013.770819","article-title":"Biochemistry and Molecular Biology of Gelatinase B or Matrix Metalloproteinase-9 (MMP-9): The next Decade","volume":"48","author":"Vandooren","year":"2013","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2119\/molmed.2009.00109","article-title":"Human Neutrophil Elastase-Mediated Cleavage Sites of MMP-9 and TIMP-1: Implications to Cystic Fibrosis Proteolytic Dysfunction","volume":"16","author":"Jackson","year":"2010","journal-title":"Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0092-8674(00)00087-8","article-title":"The Serpin A1-Proteinase Inhibitor Is a Critical Substrate for Gelatinase B\/MMP-9 In Vivo","volume":"102","author":"Liu","year":"2000","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/ppul.20165","article-title":"Induced Sputum Matrix Metalloproteinase-9 Correlates with Lung Function and Airway Inflammation in Children with Cystic Fibrosis","volume":"39","author":"Sagel","year":"2005","journal-title":"Pediatr. Pulmonol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1164\/ajrccm.152.2.7633740","article-title":"Imbalance between 95 kDa Type IV Collagenase and Tissue Inhibitor of Metalloproteinases in Sputum of Patients with Cystic Fibrosis","volume":"152","author":"Delacourt","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1136\/thorax.57.11.930","article-title":"Matrix Metalloproteases in BAL Fluid of Patients with Cystic Fibrosis and Their Modulation by Treatment with Dornase Alpha","volume":"57","author":"Ratjen","year":"2002","journal-title":"Thorax"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.1038\/s41598-021-85949-1","article-title":"Potential Novel Biomarkers for Chronic Lung Allograft Dysfunction and Azithromycin Responsive Allograft Dysfunction","volume":"11","author":"Veraar","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1183\/09031936.00212114","article-title":"Matrix Metalloproteinase Activation by Free Neutrophil Elastase Contributes to Bronchiectasis Progression in Early Cystic Fibrosis","volume":"46","author":"Garratt","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00441-016-2562-z","article-title":"Airway Mucus, Inflammation and Remodeling: Emerging Links in the Pathogenesis of Chronic Lung Diseases","volume":"367","author":"Duerr","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S172","DOI":"10.1016\/S1569-1993(11)60021-0","article-title":"The ENaC-Overexpressing Mouse as a Model of Cystic Fibrosis Lung Disease","volume":"10","author":"Zhou","year":"2011","journal-title":"J. Cyst. Fibros."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"L602","DOI":"10.1152\/ajplung.00124.2016","article-title":"Cigarette Smoke Causes Acute Airway Disease and Exacerbates Chronic Obstructive Lung Disease in Neonatal Mice","volume":"311","author":"Jia","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nm1028","article-title":"Increased Airway Epithelial Na+ Absorption Produces Cystic Fibrosis-like Lung Disease in Mice","volume":"10","author":"Mall","year":"2004","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1164\/rccm.200708-1233OC","article-title":"Development of Chronic Bronchitis and Emphysema in \u03b2-Epithelial Na+ Channel\u2013Overexpressing Mice","volume":"177","author":"Mall","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1164\/rccm.201409-1610OC","article-title":"Hypoxic Epithelial Necrosis Triggers Neutrophilic Inflammation via IL-1 Receptor Signaling in Cystic Fibrosis Lung Disease","volume":"191","author":"Fritzsching","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Johannesson, B., Hirtz, S., Schatterny, J., Schultz, C., and Mall, M.A. (2012). CFTR Regulates Early Pathogenesis of Chronic Obstructive Lung Disease in \u0392ENaC-Overexpressing Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044059"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.4049\/jimmunol.0802557","article-title":"Airway and Lung Pathology Due to Mucosal Surface Dehydration in \u03b2-Epithelial Na+ Channel-Overexpressing Mice: Role of TNF\u03b1 and IL-4R\u03b1 Signaling, Influence of Neonatal Development, and Limited Efficacy of Glucocorticoid Treatment","volume":"182","author":"Livraghi","year":"2009","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1165\/rcmb.2013-0407OC","article-title":"Airway Mucus Obstruction Triggers Macrophage Activation and MMP12-Dependent Emphysema","volume":"51","author":"Trojanek","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1900716","DOI":"10.1183\/13993003.00716-2019","article-title":"IL-17A from Innate and Adaptive Lymphocytes Contributes to Inflammation and Damage in Cystic Fibrosis Lung Disease","volume":"57","author":"Hagner","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6520","DOI":"10.1038\/s41467-021-26777-9","article-title":"Epigenetic Reprogramming of Airway Macrophages Promotes Polarization and Inflammation in Muco-Obstructive Lung Disease","volume":"12","author":"Hey","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Seys, L.J.M., Verhamme, F.M., Dupont, L.L., Desauter, E., Duerr, J., Agircan, A.S., Conickx, G., Joos, G.F., Brusselle, G.G., and Mall, M.A. (2015). Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129897"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29438","DOI":"10.1038\/srep29438","article-title":"Quantification of Heterogeneity in Lung Disease with Image-Based Pulmonary Function Testing","volume":"6","author":"Stahr","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"L401","DOI":"10.1152\/ajplung.00341.2021","article-title":"\u039cCT to Quantify Muco-Obstructive Lung Disease and Effects of Neutrophil Elastase Knockout in Mice","volume":"322","author":"Zhu","year":"2022","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1801523","DOI":"10.1183\/13993003.01523-2018","article-title":"Targeting of Cathepsin S Reduces Cystic Fibrosis-like Lung Disease","volume":"53","author":"Small","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e6682657","DOI":"10.1155\/2021\/6682657","article-title":"Therapeutic Inhibition of Cathepsin S Reduces Inflammation and Mucus Plugging in Adult \u0392ENaC-Tg Mice","volume":"2021","author":"Brown","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"L127","DOI":"10.1152\/ajplung.00047.2003","article-title":"Effects of Matrix Metalloproteinase Inhibitor on LPS-Induced Goblet Cell Metaplasia","volume":"287","author":"Kim","year":"2004","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1165\/rcmb.2010-0058OC","article-title":"A Role for Matrix Metalloproteinase 9 in IFN\u03b3-Mediated Injury in Developing Lungs","volume":"44","author":"Harijith","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"L89","DOI":"10.1152\/ajplung.00060.2012","article-title":"Molecular Mechanisms of MMP9 Overexpression and Its Role in Emphysema Pathogenesis of Smad3-Deficient Mice","volume":"303","author":"Xu","year":"2012","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"L1149","DOI":"10.1152\/ajplung.00481.2007","article-title":"Transgenic Expression of Matrix Metalloproteinase-9 Causes Adult-Onset Emphysema in Mice Associated with the Loss of Alveolar Elastin","volume":"294","author":"Foronjy","year":"2008","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1164\/rccm.201005-0718OC","article-title":"The Role of Matrix Metalloproteinase-9 in Cigarette Smoke\u2013induced Emphysema","volume":"183","author":"Atkinson","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1165\/rcmb.2007-0448OC","article-title":"Chronic LPS Inhalation Causes Emphysema-Like Changes in Mouse Lung That Are Associated with Apoptosis","volume":"39","author":"Brass","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6258","DOI":"10.1002\/anie.201109226","article-title":"Spatially Resolved Monitoring of Neutrophil Elastase Activity with Ratiometric Fluorescent Reporters","volume":"51","author":"Gehrig","year":"2012","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0092-8674(00)81169-1","article-title":"MMP-9\/Gelatinase B Is a Key Regulator of Growth Plate Angiogenesis and Apoptosis of Hypertrophic Chondrocytes","volume":"93","author":"Vu","year":"1998","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nm0598-615","article-title":"Mice Lacking Neutrophil Elastase Reveal Impaired Host Defense against Gram Negative Bacterial Sepsis","volume":"4","author":"Belaaouaj","year":"1998","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dwek, M., Brooks, S.A., and Schumacher, U. (2012). Assessment of Gelatinases (MMP-2 and MMP-9) by Gelatin Zymography. Metastasis Research Protocols, Humana Press.","DOI":"10.1007\/978-1-61779-854-2"},{"key":"ref_52","first-page":"57","article-title":"A Simple Method for Volumetry of Organs in Quantitative Stereology","volume":"26","author":"Scherle","year":"1970","journal-title":"Mikroskopie"},{"key":"ref_53","first-page":"764","article-title":"Destructive Index: A Measurement of Lung Parenchymal Destruction in Smokers","volume":"131","author":"Saetta","year":"1985","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"(1981). Stereological Methods. Vol. 1. Practical Methods for Biological Morphometry. By Ewald R. Weibel. J. Microsc., 121, 131\u2013132.","DOI":"10.1111\/j.1365-2818.1981.tb01205.x"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A New Mathematical Model for Relative Quantification in Real-Time RT\u2013PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1183\/09031936.00149810","article-title":"In Vivo Monitoring of Cystic Fibrosis-like Lung Disease in Mice by Volumetric Computed Tomography","volume":"38","author":"Eichinger","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/jappl.1964.19.1.97","article-title":"An Analysis of Pressure-Volume Characteristics of the Lungs","volume":"19","author":"Salazar","year":"1964","journal-title":"J. Appl. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13405\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:37Z","timestamp":1760144977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,2]]},"references-count":57,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232113405"],"URL":"https:\/\/doi.org\/10.3390\/ijms232113405","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,2]]}}}