{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:16:07Z","timestamp":1788243367086,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Noncommunicable Chronic Diseases\u2014National Science and Technology","award":["2024ZD0528703"],"award-info":[{"award-number":["2024ZD0528703"]}]},{"name":"1\u00b73\u00b75 Project of the State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University","award":["RHM25204"],"award-info":[{"award-number":["RHM25204"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Congenital pulmonary airway malformation (CPAM) is a rare developmental disorder characterized by cystic lung lesions, yet its extracellular matrix (ECM) composition remains poorly understood. This study employed decellularization and data-independent acquisition (DIA) proteomics to compare ECM profiles between cystic (CPAM) and histologically normal non-diseased (ND) regions from the lungs of four patients. Results: The decellularized scaffolds retained their native architecture with minimal residual DNA (&lt;50 ng\/mg). Proteomic analysis revealed 431 differentially expressed proteins (DEPs), with 171 upregulated and 260 downregulated in CPAM. Key findings revealed CPAM-specific enrichment of collagens (COL4A6, COL4A2, COL10A1, COL21A1 and PIIINP), glycoproteins (SPP1, FRAS1, FREM1, FREM2, LTBP1 and FBLN7), ECM regulators (TENM2, ROR2 and OMD), and ECM-affiliated proteins (ANXA7), alongside downregulation of glycoproteins (VASN and ABI3BP), proteoglycans (PODN and MXRA7), ECM regulators (SCARA5, PAPPA, SAA4, CPXM1, CTSC, THY1, SERPINA6\/A1\/D1, BSG, LYVE1, ITIH4 and CD44), and ECM-affiliated proteins (LGALSL). Pathway analysis highlighted the dysregulation of TGF-\u03b2, PI3K\u2013AKT, and mTOR signaling in CPAM and aberrant ECM\u2013cell interactions in pathogenesis. We also evaluated their functional properties and investigated the impact of ECM-based hydrogels on recellularization. Conclusions: These findings provide a comprehensive proteomic atlas of CPAM ECM alterations, offering insights into disease mechanisms and potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/jcm15176742","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:45:13Z","timestamp":1788241513000},"page":"6742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Composition and Function of Decellularized Human Lung Extracellular Matrix from Congenital Pulmonary Airway Malformation"],"prefix":"10.3390","volume":"15","author":[{"given":"Yanan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqiang","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-3270","authenticated-orcid":false,"given":"Ji","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7719-5983","authenticated-orcid":false,"given":"Chang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8661-4617","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/S2352-4642(18)30035-X","article-title":"Congenital pulmonary airway malformation: Advances and controversies","volume":"2","author":"Wong","year":"2018","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151228","DOI":"10.1016\/j.sempedsurg.2022.151228","article-title":"Congenital lung malformations: Dysregulated lung developmental processes and altered signaling pathways","volume":"31","author":"Doktor","year":"2022","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/ppul.25785","article-title":"A national descriptive epidemiologic analysis on congenital pulmonary airway malformation in China, 2010\u20132019","volume":"57","author":"Xu","year":"2022","journal-title":"Pediatr. Pulmonol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"L144","DOI":"10.1152\/ajplung.00379.2017","article-title":"Human lung branching morphogenesis is orchestrated by the spatiotemporal distribution of ACTA2, SOX2, and SOX9","volume":"314","author":"Danopoulos","year":"2018","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1164\/rccm.201706-1243OC","article-title":"Novel Molecular and Phenotypic Insights into Congenital Lung Malformations","volume":"197","author":"Swarr","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41572-023-00470-1","article-title":"Congenital lung malformations","volume":"9","author":"Pederiva","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.matbio.2018.03.005","article-title":"Extracellular matrix in lung development, homeostasis and disease","volume":"73","author":"Zhou","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1165\/rcmb.2023-0176PS","article-title":"Extracellular Matrix as a Driver of Chronic Lung Diseases","volume":"70","author":"Burgess","year":"2024","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"210202","DOI":"10.1183\/16000617.0202-2021","article-title":"Chronic lung diseases: Entangled in extracellular matrix","volume":"31","author":"Burgess","year":"2022","journal-title":"Eur. Respir. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41580-024-00767-3","article-title":"Mechanisms of assembly and remodelling of the extracellular matrix","volume":"25","author":"Naba","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4289","DOI":"10.1016\/j.cell.2024.05.057","article-title":"The extracellular matrix integrates mitochondrial homeostasis","volume":"187","author":"Zhang","year":"2024","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1016\/j.cell.2025.03.011","article-title":"From geroscience to precision geromedicine: Understanding and managing aging","volume":"188","author":"Kroemer","year":"2025","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"670","DOI":"10.14336\/AD.2022.1116","article-title":"Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity","volume":"14","author":"Statzer","year":"2023","journal-title":"Aging Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1601805","DOI":"10.1183\/13993003.01805-2016","article-title":"The instructive extracellular matrix of the lung: Basic composition and alterations in chronic lung disease","volume":"50","author":"Burgstaller","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"190124","DOI":"10.1183\/16000617.0124-2019","article-title":"Extracellular matrix remodelling in COPD","volume":"29","author":"Karakioulaki","year":"2020","journal-title":"Eur. Respir. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1172\/JCI93557","article-title":"Extracellular matrix as a driver of progressive fibrosis","volume":"128","author":"Herrera","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.actbio.2019.11.029","article-title":"Functional role of glycosaminoglycans in decellularized lung extracellular matrix","volume":"102","author":"Uhl","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121960","DOI":"10.1016\/j.biomaterials.2022.121960","article-title":"Regional and disease specific human lung extracellular matrix composition","volume":"293","author":"Hoffman","year":"2022","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.actbio.2023.06.043","article-title":"Regional and disease-specific glycosaminoglycan composition and function in decellularized human lung extracellular matrix","volume":"168","author":"HoHoffman","year":"2023","journal-title":"Acta Biomater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/jbm.a.37158","article-title":"Decellularization of porcine whole lung to obtain a clinical-scale bioengineered scaffold","volume":"109","author":"Li","year":"2021","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/jcb.30216","article-title":"Global interpretation of novel alternative splicing events in human congenital pulmonary airway malformations: A pilot study","volume":"123","author":"Yang","year":"2022","journal-title":"J. Cell Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s12931-023-02436-z","article-title":"Integrated bulk and single-cell RNA-sequencing reveals SPOCK2 as a novel biomarker gene in the development of congenital pulmonary airway malformation","volume":"24","author":"Tan","year":"2023","journal-title":"Respir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1038\/s41598-024-54924-x","article-title":"The underlying molecular mechanism of ciliated epithelium dysfunction and TGF-\u03b2 signaling in children with congenital pulmonary airway malformations","volume":"14","author":"Zhang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13578-024-01276-8","article-title":"Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM","volume":"14","author":"Li","year":"2024","journal-title":"Cell Biosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5296","DOI":"10.1038\/s41598-019-41777-y","article-title":"Alteration of cystic airway mesenchyme in congenital pulmonary airway malformation","volume":"9","author":"Jiang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s13023-019-1192-4","article-title":"New insights on congenital pulmonary airways malformations revealed by proteomic analyses","volume":"14","author":"Maillard","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s12931-025-03332-4","article-title":"Atypical mesenchyme in congenital pulmonary airways malformation: A promising new focus","volume":"26","author":"Azar","year":"2025","journal-title":"Respir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Huang, J., Chen, Q., Hong, S., Hong, J., and Cao, H. (2025). Single-cell sequencing reveals cellular differences and potential mechanisms in congenital pulmonary airway malformation. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1548177"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112299","DOI":"10.1016\/j.yexcr.2020.112299","article-title":"Single-cell transcriptome profiling reveals the mechanism of abnormal proliferation of epithelial cells in congenital cystic adenomatoid malformation","volume":"396","author":"Zhang","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Beck, T.F., Shchelochkov, O.A., Yu, Z., Kim, B.J., Hern\u00e1ndez-Garc\u00eda, A., Zaveri, H.P., Bishop, C., Overbeek, P.A., Stockton, D.W., and Justice, M.J. (2013). Novel frem1-related mouse phenotypes and evidence of genetic interactions with gata4 and slit3. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058830"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"L1134","DOI":"10.1152\/ajplung.00022.2004","article-title":"RhoA and Rac1 are both required for efficient wound closure of airway epithelial cells","volume":"287","author":"Desai","year":"2004","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1165\/rcmb.2024-0140OC","article-title":"KLF5 Shapes Developing Respiratory Tubules by Inhibiting Actin Asymmetry in Epithelial Cells","volume":"72","author":"Li","year":"2024","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zeng, J., Liu, W., Liang, J., Peng, J., Wang, F., Tang, J., Yang, Q., Zhuang, L., Huang, D., and Li, L. (2021). Analysis of miRNA Profiles and the Regulatory Network in Congenital Pulmonary Airway Malformations. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.671107"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20459","DOI":"10.1038\/s41598-022-24858-3","article-title":"Application of second-generation sequencing in congenital pulmonary airway malformations","volume":"12","author":"Zhang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"L1158","DOI":"10.1152\/ajplung.00299.2020","article-title":"Abrogation of mesenchyme-specific TGF-\u03b2 signaling results in lung malformation with prenatal pulmonary cysts in mice","volume":"320","author":"Miao","year":"2021","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12931-020-1306-5","article-title":"Congenital cystic adenomatoid malformations of the lung: An epithelial transcriptomic approach","volume":"21","author":"Lezmi","year":"2020","journal-title":"Respir. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Patrizi, S., Pederiva, F., and D\u2019aDamo, A.P. (2021). Whole-Genome Methylation Study of Congenital Lung Malformations in Children. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.689833"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/s41578-023-00551-3","article-title":"Extracellular vesicle-matrix interactions","volume":"8","author":"Debnath","year":"2023","journal-title":"Nat. Rev. Mater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e72638","DOI":"10.1002\/hsr2.72638","article-title":"Multifaceted Role of Extracellular Vesicles: Intercellular Messengers to Therapeutic Applications: A Narrative Review","volume":"9","author":"Kamra","year":"2026","journal-title":"Health Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12964-025-02630-0","article-title":"The interplay between the extracellular matrix and extracellular vesicle-associated microRNAs","volume":"24","author":"Wu","year":"2026","journal-title":"Cell Commun. Signal"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100274","DOI":"10.1016\/j.mtbio.2022.100274","article-title":"Ordered micropattern arrays fabricated by lung-derived dECM hydrogels for chemotherapeutic drug screening","volume":"15","author":"Zhu","year":"2022","journal-title":"Mater. Today Bio"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"015037","DOI":"10.1088\/1758-5090\/ada092","article-title":"Lung dECM matrikine-based hydrogel reverses bleomycin-induced pulmonary fibrosis by suppressing M2 macrophage polarization","volume":"17","author":"Zhu","year":"2024","journal-title":"Biofabrication"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1021\/acsnano.4c11113","article-title":"Biomimetic Topological Micropattern Arrays Regulate the Heterogeneity of Cellular Fates in Lung Fibroblasts between Fibrosis and Invasion","volume":"19","author":"Zhu","year":"2025","journal-title":"ACS Nano"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6742\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:56:14Z","timestamp":1788242174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":43,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15176742"],"URL":"https:\/\/doi.org\/10.3390\/jcm15176742","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,30]]}}}