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Cited by 74Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisOccupational and environmental lung diseasesAdvanced Proteomics Techniques and Applications

Quantitative proteomic characterization of lung tissue in idiopathic pulmonary fibrosis

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Tian, Yaqiong, Li, Hui, Gao, Yujuan, Liu, Chuanmei, Qiu, Ting, Wu, Hongyan, Cao, Mengshu, Zhang, Yingwei +3 more·2019·Clinical Proteomics
DOI 10.1186/s12014-019-9226-4PMC PMC6364390
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Abstract

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and progressive lung scarring. The pathogenesis of IPF and whether the ECM involved in the process remain unknown. METHODS: To identify potential treatment target and ECM associated proteins that may be involved in the development of IPF, we employed isobaric tag for relative and absolute quantitation (iTRAQ) combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to examine protein expression in lung tissues from IPF patients. RESULTS: A total of 662 proteins with altered expression (455 upregulated proteins and 207 downregulated proteins) were identified in lung tissue of IPF patients compared with control. KEGG pathway enrichment analysis showed that the altered proteins in lung tissue mainly belonged to the PI3K-Akt signaling, focal adhesion, ECM-receptor interaction, and carbon metabolism pathways. According to the bioinformatic definition of the matrisome, 229 matrisome proteins were identified in lung tissue. These proteins comprised the ECM of lung, of which 104 were core matrisome proteins, and 125 were matrisome-associated proteins. Of the 229 ECM quantified proteins, 56 significantly differentially expressed proteins (19 upregulated proteins and 37 downregulated proteins) were detected in IPF lung tissue samples. In addition to proteins with well-known functions such as COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, we identified several novel ECM proteins with unknown function deposited in IPF lung tissue including LGALS7, ASPN, HSP90AA1 and HSP90AB1. Some of these differentially expressed proteins were further verified using Western blot analysis and immunohistochemical staining. CONCLUSIONS: This study provides a list of proteomes that were detected in IPF lung tissue by iTRAQ technology combined with LC-MS/MS. The findings of this study will contribute better understanding to the pathogenesis of IPF and facilitate the development of therapeutic targets.

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  • Cav-1 expression in pulmonary fibroblasts and alveolar epithelial cells is decreased in transgenic and rodent bleomycin models of lung injury and in the lungs of patients with IPF.

    “Cav-1 expression in pulmonary fibroblasts and alveolar epithelial cells is decreased in transgenic and rodent bleomycin models of lung injury and in the lungs of patients with IPF10–12.”

    From Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study (2026) · cites this paper as [12]

    The Results section (Validation of differentially expressed proteins; page not provided) reports that CAV1 staining in alveolar epithelial cells was strong in control lungs but almost absent in IPF lungs. Our copy does not establish decreased CAV1 in pulmonary fibroblasts or in transgenic or rodent bleomycin lung-injury models. (LLM, conf=0.88)

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  • Immunohistochemical analyses of IPF lung tissue have shown intense GAL-7 expression localized to the alveolar and bronchiolar epithelium and alveolar septum.

    “Immunohistochemical analyses of IPF lung tissue have shown intense GAL-7 expression localized to the alveolar and bronchiolar epithelium and alveolar septum12.”

    From Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study (2026) · cites this paper as [12]

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Research works printed but not linked: 48

  1. [1]Raghu G Collard HR Egan JJ Martinez FJ Behr J An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management Am J Respir Crit Care Med 2011 183 6 788 824 10.1164/rccm.2009-040GL 21471066 PMC5450933 · DOI · Paper page
  2. [2]Travis WD Costabel U Hansell DM King TE Jr Lynch DA An official American thoracic society/European respiratory society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias Am J Respir Crit Care Med 2013 188 6 733 748 10.1164/rccm.201308-1483ST 24032382 PMC5803655 · DOI
  3. [3]Raghu G Rochwerg B Zhang Y Garcia CA Azuma A An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline Am J Respir Crit Care Med 2015 192 2 e3 19 10.1164/rccm.201506-1063ST 26177183 · DOI · Paper page
  4. [4]Fernandez IE Eickelberg O New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis Lancet 2012 380 9842 680 688 10.1016/S0140-6736(12)61144-1 22901889 · DOI
  5. [5]Sgalla G Iovene B Calvello M Ori M Varone F Idiopathic pulmonary fibrosis: pathogenesis and management Respir Res 2018 19 1 32 10.1186/s12931-018-0730-2 29471816 PMC5824456 · DOI · Paper page
  6. [6]Kan M Shumyatcher M Himes BE Using omics approaches to understand pulmonary diseases Respir Res 2017 18 1 149 10.1186/s12931-017-0631-9 28774304 PMC5543452 · DOI
  7. [7]Goodwin AT Jenkins G Molecular endotyping of pulmonary fibrosis Chest 2016 149 1 228 237 10.1378/chest.15-1511 26356594 · DOI
  8. [8]Hambly N Shimbori C Kolb M Molecular classification of idiopathic pulmonary fibrosis: personalized medicine, genetics and biomarkers Respirology 2015 20 7 1010 1022 10.1111/resp.12569 26109466 · DOI
  9. [9]Huang Y Ma SF Vij R Oldham JM Herazo-Maya J A functional genomic model for predicting prognosis in idiopathic pulmonary fibrosis BMC Pulm Med 2015 15 147 10.1186/s12890-015-0142-8 26589497 PMC4654815 · DOI
  10. [10]Seibold MA Wise AL Speer MC Steele MP Brown KK A common MUC5B promoter polymorphism and pulmonary fibrosis N Engl J Med 2011 364 16 1503 1512 10.1056/NEJMoa1013660 21506741 PMC3379886 · DOI
  11. [11]Peljto AL Zhang Y Fingerlin TE Ma SF Garcia JG Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis JAMA 2013 309 21 2232 2239 10.1001/jama.2013.5827 23695349 PMC4545271 · DOI
  12. [12]Konishi K Gibson KF Lindell KO Richards TJ Zhang Y Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis Am J Respir Crit Care Med 2009 180 2 167 175 10.1164/rccm.200810-1596OC 19363140 PMC2714820 · DOI
  13. [13]Selman M Pardo A Barrera L Estrada A Watson SR Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis Am J Respir Crit Care Med 2006 173 2 188 198 10.1164/rccm.200504-644OC 16166619 PMC2662988 · DOI
  14. [14]Yang IV Burch LH Steele MP Savov JD Hollingsworth JW Gene expression profiling of familial and sporadic interstitial pneumonia Am J Respir Crit Care Med 2007 175 1 45 54 10.1164/rccm.200601-062OC 16998095 PMC1899261 · DOI
  15. [15]Herazo-Maya JD Noth I Duncan SR Kim S Ma SF Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis Sci Transl Med 2013 5 205 205ra136 10.1126/scitranslmed.3005964 PMC4175518 24089408 · DOI · Paper page
  16. [16]Sun N Fernandez IE Wei M Witting M Aichler M Pharmacometabolic response to pirfenidone in pulmonary fibrosis detected by MALDI-FTICR-MSI Eur Respir J 2018 52 3 1702314 10.1183/13993003.02314-2017 30072508 · DOI
  17. [17]Zhang Y Xin Q Wu Z Wang C Wang Y Application of isobaric tags for relative and absolute quantification (iTRAQ) coupled with two-dimensional liquid chromatography/tandem mass spectrometry in quantitative proteomic analysis for discovery of serum biomarkers for idiopathic pulmonary fibrosis Med Sci Monit 2018 24 4146 4153 10.12659/MSM.908702 29909421 PMC6036962 · DOI
  18. [18]Niu R Liu Y Zhang Y Zhang Y Wang H iTRAQ-based proteomics reveals novel biomarkers for idiopathic pulmonary fibrosis PLoS ONE 2017 12 1 e0170741 10.1371/journal.pone.0170741 28122020 PMC5266322 · DOI
  19. [19]Schiller HB Mayr CH Leuschner G Strunz M Staab-Weijnitz C Deep proteome profiling reveals common prevalence of MZB1-positive plasma B cells in human lung and skin fibrosis Am J Respir Crit Care Med 2017 196 10 1298 1310 10.1164/rccm.201611-2263OC 28654764 PMC6913086 · DOI
  20. [20]Yu G Ibarra GH Kaminski N Fibrosis: lessons from OMICS analyses of the human lung Matrix Biol 2018 68–69 422 434 10.1016/j.matbio.2018.03.014 PMC6015529 29567123 · DOI
  21. [21]Knudsen L Ruppert C Ochs M Tissue remodelling in pulmonary fibrosis Cell Tissue Res 2017 367 3 607 626 10.1007/s00441-016-2543-2 27981380 · DOI
  22. [22]Herrera J Henke CA Bitterman PB Extracellular matrix as a driver of progressive fibrosis J Clin Invest 2018 128 1 45 53 10.1172/JCI93557 29293088 PMC5749528 · DOI
  23. [23]Korfei M Schmitt S Ruppert C Henneke I Markart P Comparative proteomic analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and lung transplant donor lungs J Proteome Res 2011 10 5 2185 2205 10.1021/pr1009355 21319792 · DOI
  24. [24]Booth AJ Hadley R Cornett AM Dreffs AA Matthes SA Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation Am J Respir Crit Care Med 2012 186 9 866 876 10.1164/rccm.201204-0754OC 22936357 PMC3530219 · DOI · Paper page
  25. [25]Korfei M Von Der Beck D Henneke I Markart P Ruppert C Comparative proteome analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and organ donors J Proteom 2013 85 109 128 10.1016/j.jprot.2013.04.033 23659799 · DOI
  26. [26]Ahrman E Hallgren O Malmstrom L Hedstrom U Malmstrom A Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis J Proteom 2018 189 23 33 10.1016/j.jprot.2018.02.027 29501846 · DOI · Paper page
  27. [27]Burgess JK Mauad T Tjin G Karlsson JC Westergren-Thorsson G The extracellular matrix—the under-recognized element in lung disease? J Pathol 2016 240 4 397 409 10.1002/path.4808 27623753 PMC5129494 · DOI
  28. [29]Naba A Clauser KR Hoersch S Liu H Carr SA The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices Mol Cell Proteom 2012 11 4 M111.014647 10.1074/mcp.M111.014647 PMC3322572 22159717 · DOI · Paper page
  29. [31]Tsujino K Takeda Y Arai T Shintani Y Inagaki R Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity Am J Respir Crit Care Med 2012 186 2 170 180 10.1164/rccm.201201-0117OC 22592804 PMC5448656 · DOI
  30. [32]Yu H Konigshoff M Jayachandran A Handley D Seeger W Transgelin is a direct target of TGF-beta/Smad3-dependent epithelial cell migration in lung fibrosis Faseb J 2008 22 6 1778 1789 10.1096/fj.07-083857 18245174 · DOI
  31. [33]Buendia-Roldan I Ruiz V Sierra P Montes E Ramirez R Increased expression of CC16 in patients with idiopathic pulmonary fibrosis PLoS ONE 2016 11 12 e0168552 10.1371/journal.pone.0168552 27977812 PMC5158056 · DOI
  32. [34]Kasabova M Joulin-Giet A Lecaille F Gilmore BF Marchand-Adam S Regulation of TGF-beta1-driven differentiation of human lung fibroblasts: emerging roles of cathepsin B and cystatin C J Biol Chem 2014 289 23 16239 16251 10.1074/jbc.M113.542407 24790080 PMC4047393 · DOI
  33. [35]Canbay A Guicciardi ME Higuchi H Feldstein A Bronk SF Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis J Clin Invest 2003 112 2 152 159 10.1172/JCI200317740 12865404 PMC164289 · DOI
  34. [36]Moles A Tarrats N Fernandez-Checa JC Mari M Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential Hepatology 2009 49 4 1297 1307 10.1002/hep.22753 19116891 PMC2670444 · DOI
  35. [37]Chen H Wang J Xiang MX Lin Y He A Cathepsin S-mediated fibroblast trans-differentiation contributes to left ventricular remodelling after myocardial infarction Cardiovasc Res 2013 100 1 84 94 10.1093/cvr/cvt158 23771947 PMC3778959 · DOI
  36. [38]Bellaye PS Shimbori C Yanagihara T Carlson DA Synergistic role of HSP90alpha and HSP90beta to promote myofibroblast persistence in lung fibrosis Eur Respir J 2018 51 2 1700386 10.1183/13993003.00386-2017 29386344 · DOI
  37. [39]Calabrese F Lunardi F Giacometti C Marulli G Gnoato M Overexpression of squamous cell carcinoma antigen in idiopathic pulmonary fibrosis: clinicopathological correlations Thorax 2008 63 9 795 802 10.1136/thx.2007.088583 18344408 · DOI
  38. [40]Verrecchia F Chu ML Mauviel A Identification of novel TGF-beta/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach J Biol Chem 2001 276 20 17058 17062 10.1074/jbc.M100754200 11279127 · DOI
  39. [41]Mcleod K Walker JT Hamilton DW Galectin-3 regulation of wound healing and fibrotic processes: insights for chronic skin wound therapeutics J Cell Commun Signal 2018 12 1 281 287 10.1007/s12079-018-0453-7 29372416 PMC5842207 · DOI
  40. [42]Kathiriya JJ Nakra N Nixon J Patel PS Vaghasiya V Galectin-1 inhibition attenuates profibrotic signaling in hypoxia-induced pulmonary fibrosis Cell Death Discov 2017 3 17010 10.1038/cddiscovery.2017.10 28417017 PMC5385413 · DOI
  41. [43]Mackinnon AC Gibbons MA Farnworth SL Leffler H Nilsson UJ Regulation of transforming growth factor-beta1-driven lung fibrosis by galectin-3 Am J Respir Crit Care Med 2012 185 5 537 546 10.1164/rccm.201106-0965OC 22095546 PMC3410728 · DOI
  42. [44]Gendronneau G Sidhu SS Delacour D Dang T Calonne C Galectin-7 in the control of epidermal homeostasis after injury Mol Biol Cell 2008 19 12 5541 5549 10.1091/mbc.e08-02-0166 18829868 PMC2592666 · DOI
  43. [45]Advedissian T Deshayes F Viguier M Galectin-7 in epithelial homeostasis and carcinomas Int J Mol Sci 2017 18 12 E2760 10.3390/ijms18122760 29257082 PMC5751359 · DOI
  44. [46]Inagaki Y Higashi K Kushida M Hong YY Nakao S Hepatocyte growth factor suppresses profibrogenic signal transduction via nuclear export of Smad3 with galectin-7 Gastroenterology 2008 134 4 1180 1190 10.1053/j.gastro.2008.01.014 18395096 · DOI
  45. [47]Calle EA Hill RC Leiby KL Le AV Gard AL Targeted proteomics effectively quantifies differences between native lung and detergent-decellularized lung extracellular matrices Acta Biomater 2016 46 91 100 10.1016/j.actbio.2016.09.043 27693690 PMC5451113 · DOI
  46. [48]Krasny L Bland P Kogata N Wai P Howard BA SWATH mass spectrometry as a tool for quantitative profiling of the matrisome J Proteom 2018 189 11 22 10.1016/j.jprot.2018.02.026 PMC6215756 29501709 · DOI
  47. [49]Krasny L Paul A Wai P Howard BA Natrajan RC Comparative proteomic assessment of matrisome enrichment methodologies Biochem J 2016 473 21 3979 3995 10.1042/BCJ20160686 27589945 PMC5095915 · DOI
  48. [50]Chanda D Otoupalova E Hough KP Locy ML Bernard K Fibronectin on the surface of extracellular vesicles mediates fibroblast invasion Am J Respir Cell Mol Biol. 2018 10.1165/rcmb.2018-0062OC 30321056 PMC6397976 · DOI

Cited by

Sorted by citations

Authors
Tian, Y., Li, H., Gao, Y., Liu, C., Qiu, T., Wu, H., Cao, M., Zhang, Y., Ding, H., Chen, J., & Cai, H.
Affiliations
  • Nanjing Drum Tower Hospital (CN)
  • Wannan Medical College (CN)
  • Traditional Chinese Medicine Hospital of Kunshan (CN)
  • Jiangsu University (CN)
  • Wuxi People's Hospital (CN)
Corresponding author
  • Chen, Jingyu
  • Cai, Hourong
ORCID
Venue
Clinical Proteomics
Publisher
Springer Science and Business Media LLC
Published
2019-02-06
Volume
16
Issue
1
Pages
6-6
ISSN
  • 1542-6416 (ISSN-L)
  • 1559-0275
DOI
10.1186/s12014-019-9226-4
PMC
PMC6364390
OpenAlex
W2922148620
Cited by
74
References
2
Citations by year
2026: 9 · 2025: 13 · 2024: 2 · 2023: 15 · 2022: 12 · 2021: 8 · 2020: 11 · 2019: 4
FWCI
6.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Proteomics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Jiangsu Provincial Key research and developmen (BE2016611)
  • National Natural Science Foundation of China (81670058, 81470253, 81570055, 81670059)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
idiopathic pulmonary fibrosis, lung proteome, extracellular matrix, matrisome, differentially expressed proteins, PI3K/Akt signaling, focal adhesions, ECM-receptor interaction, lung scarring, therapeutic target, iTRAQ quantification

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