Role of matrix metalloproteases in pulmonary fibrosis

  • Annie Pardo
  • Moisés Selman
Part of the Progress in Inflammation Research book series (PIR)


Lung fibrosis is the final result of a large variety of stimuli including systemic and autoimmune reactions, exposure to organic and inorganic particles, drugs, and radiation. Independent of etiology, the fibrotic response in the lung can be visualized as a dynamic and highly integrated cellular response to persistent injury and may be related to a damage-triggered inflammatory response or to an aberrant epithelial or endothelial reaction. In any case, the key cellular mediator is the myofibroblast, which when activated is the major effector of the lung remodeling. Several matrix metalloproteases (MMPs) have been shown to participate in this pathological process. These enzymes play an essential but complex role in several interrelated processes that take place in the pathogenesis of lung fibrosis including extracellular matrix remodeling, basement membrane disruption, epithelial apoptosis, cell migration, and angiogenesis. This review will focus on the role of MMPs in the development of lung fibrosis.


Idiopathic Pulmonary Fibrosis Pulmonary Fibrosis Interstitial Lung Disease Respir Crit Alveolar Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Ryu JH, Daniels CE, Hartman TE, Yi ES (2007) Diagnosis of interstitial lung diseases. Mayo Clin Proc 82: 976–986PubMedGoogle Scholar
  2. 2.
    Green FH (2002) Overview of pulmonary fibrosis. Chest 122(6 Suppl): 334S–339SPubMedCrossRefGoogle Scholar
  3. 3.
    Pardo A, Selman M (2002) Molecular mechanisms of pulmonary fibrosis. Front Biosci 7: d1743–1761PubMedCrossRefGoogle Scholar
  4. 4.
    Selman M, King TE, Pardo A (2001) Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 134: 136–151PubMedGoogle Scholar
  5. 5.
    Luzina IG, Todd NW, Iacono AT, Atamas SP (2008) Roles of T lymphocytes in pulmonary fibrosis. J Leukoc Biol 83: 237–244PubMedCrossRefGoogle Scholar
  6. 6.
    Stramer BM, Mori R, Martin P (2007) The inflammation-fibrosis link? A Jekyll and Hyde role for blood cells during wound repair. J Invest Dermatol 127: 1009–1017PubMedCrossRefGoogle Scholar
  7. 7.
    Huaux F (2007) New developments in the understanding of immunology in silicosis. Curr Opin Allergy Clin Immunol 7: 168–173PubMedCrossRefGoogle Scholar
  8. 8.
    Keane MP, Strieter RM, Lynch JP 3rd, Belperio JA (2006) Inflammation and angiogenesis in fibrotic lung disease. Semin Respir Crit Care Med 27: 589–599PubMedCrossRefGoogle Scholar
  9. 9.
    Garrood T, Lee L, Pitzalis C (2006) Molecular mechanisms of cell recruitment to inflammatory sites: general and tissue-specific pathways. Rheumatology (Oxford) 45: 250–260CrossRefGoogle Scholar
  10. 10.
    Rao RM, Shaw SK, Kim M, Luscinskas FW (2005) Emerging topics in the regulation of leukocyte transendothelial migration. Microcirculation 12: 83–89PubMedCrossRefGoogle Scholar
  11. 11.
    Selman M, Pardo A (2006) Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers. Proc Am Thorac Soc 3: 364–372PubMedCrossRefGoogle Scholar
  12. 12.
    Lee JM, Dedhar S, Kalluri R, Thompson EW (2006) The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172: 973–981PubMedCrossRefGoogle Scholar
  13. 13.
    Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, du Bois RM, Borok Z (2005) Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol 166: 1321–1332PubMedGoogle Scholar
  14. 14.
    Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, Sheppard D, Chapman HA (2006) Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA 103: 13180–13185PubMedCrossRefGoogle Scholar
  15. 15.
    Rawlings ND, Morton FR, Barrett AJ (2006) MEROPS: the peptidase database. Nucleic Acids Res 34: D270–D272PubMedCrossRefGoogle Scholar
  16. 16.
    Pardo A, Selman M, Kaminski N (2008) Approaching the degradome in idiopathic pulmonary fibrosis. Int J Biochem Cell Biol 40: 1141–1155PubMedCrossRefGoogle Scholar
  17. 17.
    Puente XS, Sanchez LM, Overall CM, Lopez-Otin C (2003) Human and mouse proteases: a comparative genomic approach. Nat Rev Genet 4: 544–558PubMedCrossRefGoogle Scholar
  18. 18.
    Limb GA, Matter K, Murphy G, Cambrey AD, Bishop PN, Morris GE, Khaw PT (2005) Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. Am J Pathol 166: 1555–1563PubMedGoogle Scholar
  19. 19.
    Wang W, Schulze CJ, Suarez-Pinzon WL, Dyck JR, Sawicki G, Schulz R (2002) Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury. Circulation 106: 1543–1549PubMedCrossRefGoogle Scholar
  20. 20.
    Kwan JA, Schulze CJ, Wang W, Leon H, Sariahmetoglu M, Sung M, Sawicka J, Sims DE, Sawicki G, Schulz R (2004) Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro. FASEB J 18: 690–692PubMedGoogle Scholar
  21. 21.
    Luo D, Mari B, Stoll I, Anglard P (2002) Alternative splicing and promoter usage generates an intracellular stromelysin 3 isoform directly translated as an active matrix metalloproteinase. J Biol Chem 277: 25527–25536PubMedCrossRefGoogle Scholar
  22. 22.
    Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3: 207–214PubMedCrossRefGoogle Scholar
  23. 23.
    Folgueras AR, Pendas AM, Sanchez LM, Lopez-Otin C (2004) Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol 48: 411–424PubMedCrossRefGoogle Scholar
  24. 24.
    Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17: 463–516PubMedCrossRefGoogle Scholar
  25. 25.
    Pardo A, Selman M (2006) Matrix metalloproteases in aberrant fibrotic tissue remodeling. Proc Am Thorac Soc 3: 383–388PubMedCrossRefGoogle Scholar
  26. 26.
    Zuo F, Kaminski N, Eugui E, Allard J, Yakhini Z, Ben-Dor A, Lollini L, Morris D, Kim Y, DeLustro B et al (2002) Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc Natl Acad Sci USA 999: 6292–6297CrossRefGoogle Scholar
  27. 27.
    Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M (2000) Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 117: 684–694PubMedCrossRefGoogle Scholar
  28. 28.
    Vincenti MP, Brinckerhoff CE (2002) Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res 4: 157–164PubMedCrossRefGoogle Scholar
  29. 29.
    Fukuda Y, Ishizaki M, Kudoh S, Kitaichi M, Yamanaka N (1998) Localization of matrix metalloproteinases-1,-2, and-9 and tissue inhibitor of metalloproteinase-2 in interstitial lung diseases. Lab Invest 78: 687–698PubMedGoogle Scholar
  30. 30.
    Selman M, Ruiz V, Cabrera S, Segura L, Ramírez R, Barrios R, Pardo A (2000) TIMP-1,-2,-3 and-4 in idiopathic pulmonary fibrosis. A prevailing non degradative lung microenvironment? Am J Physiol 279: L562–L574Google Scholar
  31. 31.
    Hall MC, Young DA, Waters JG, Rowan AD, Chantry A, Edwards DR, Clark IM (2003) The comparative role of activator protein 1 and Smad factors in the regulation of Timp-1 and MMP-1 gene expression by transforming growth factor-beta 1. J Biol Chem 278: 10304–10313PubMedCrossRefGoogle Scholar
  32. 32.
    Pardo A, Gibson K, Cisneros J, Richards TJ, Yang Y, Becerril C, Yousem S, Herrera I, Ruiz V, Selman M et al (2005) Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis. PLoS Med 2: e251PubMedCrossRefGoogle Scholar
  33. 33.
    Swiderski RE, Dencoff JE, Floerchinger CS, Shapiro SD, Hunninghake GW (1998) Differential expression of extracellular matrix remodeling genes in a murine model of bleomycin-induced pulmonary fibrosis. Am J Pathol 152: 821–828PubMedGoogle Scholar
  34. 34.
    Ortiz LA, Lasky J, Gozal E, Ruiz V, Lungarella G, Cavarra E, Brody AR, Friedman M, Pardo A, Selman M (2001) Tumor necrosis factor receptor deficiency alters matriz metalloproteinase 13/tissue inhibitor of metalloproteinase 1 expression in murine silicosis. Am J Respir Crit Care Med 163: 244–252PubMedGoogle Scholar
  35. 35.
    Ruiz V, Ordonez RM, Berumen J, Ramirez R, Uhal B, Becerril C, Pardo A, Selman M (2003) Unbalanced collagenase/TIMP-1 expression and epithelial apoptosis in experimental lung fibrosis. Am J Physiol Lung Cell Mol Physiol 285: L1026–1036PubMedGoogle Scholar
  36. 36.
    D’Armiento J, Dalal SS, Okada Y, Berg RA, Chada K (1992) Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 71: 955–961PubMedCrossRefGoogle Scholar
  37. 37.
    Pilcher BK, Dumin JA, Sudbeck BD, Krane SM, Welgus HG, Parks WC (1997) The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix. J Cell Biol 137: 1445–1457PubMedCrossRefGoogle Scholar
  38. 38.
    Selman M, Pardo A, Barrera L, Estrada A, Watson SR, Wilson K, Aziz N, Kaminski N, Zlotnik A (2006) Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. Am J Respir Crit Care Med 173: 188–198PubMedCrossRefGoogle Scholar
  39. 39.
    Vuorinen K, Myllarniemi M, Lammi L, Piirila P, Rytila P, Salmenkivi K, Kinnula VL (2007) Elevated matrilysin levels in bronchoalveolar lavage fluid do not distinguish idiopathic pulmonary fibrosis from other interstitial lung diseases. APMIS 115, 969–975PubMedCrossRefGoogle Scholar
  40. 40.
    Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L (2001) Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem 276: 28261–28267PubMedCrossRefGoogle Scholar
  41. 41.
    Li Q, Park PW, Wilson CL, Parks WC (2002) Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 111: 635–646PubMedCrossRefGoogle Scholar
  42. 42.
    Patterson ML, Atkinson SJ, Knäuper V, Murphy G (2001) Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectinlike domain. FEBS Lett 503: 158–162PubMedCrossRefGoogle Scholar
  43. 43.
    McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM (2000) Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289: 1202–1206PubMedCrossRefGoogle Scholar
  44. 44.
    Monaco S, Sparano V, Gioia M, Sbardella D, Di Pierro D, Marini S, Coletta M (2006) Enzymatic processing of collagen IV by MMP-2 (gelatinase A) affects neutrophil migration and it is modulated by extracatalytic domains. Protein Sci 15: 2805–2815PubMedCrossRefGoogle Scholar
  45. 45.
    Hayashi T, Stetler-Stevenson WG, Fleming MV, Fishback N, Koss MN, Liotta LA, Ferrans VJ, Travis WD (1996) Immunohistochemical study of metalloproteinases and their tissue inhibitors in the lungs of patients with diffuse alveolar damage and idiopathic pulmonary fibrosis. Am J Pathol 149: 1241–1256PubMedGoogle Scholar
  46. 46.
    García-Alvarez J, Ramirez R, Sampieri CL, Nuttall RK, Edwards DR, Selman M, Pardo A (2006) Membrane type-matrix metalloproteinases in idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 23: 13–21PubMedGoogle Scholar
  47. 47.
    Van den Steen PE, Van Aelst I, Hvidberg V, Piccard H, Fiten P, Jacobsen C, Moestrup SK, Fry S, Royle L, Wormald MR et al (2006) The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. J Biol Chem 281: 18626–18637PubMedCrossRefGoogle Scholar
  48. 48.
    Pérez-Ramos J, Segura L, Ramírez R, Vanda B, Selman M, Pardo A (1999) Matrix metalloproteinases 2, 9, and 13 and tissue inhibitor of metalloproteinases 1 and 2 in early and late lesions of experimental lung silicosis. Am J Respir Crit Care Med 160: 1274–1282PubMedGoogle Scholar
  49. 49.
    Cisneros-Lira J, Gaxiola M, Ramos C, Selman M, Pardo A (2003) Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs. Am J Physiol Lung Cell Mol Physiol 285: L949–956PubMedGoogle Scholar
  50. 50.
    Pardo A, Ruiz V, Arreola JL, Ramírez R, Cisneros-Lira J, Gaxiola M, Barrios R, Kala SV, Lieberman MW, Selman M (2003) Bleomycin-induced pulmonary fibrosis is attenuated in g_glutamyl transpeptidase-deficient mice. Am J Respir Crit Care Med 167: 925–932PubMedCrossRefGoogle Scholar
  51. 51.
    Selman M, Carrillo G, Estrada A, Mejia M, Becerril C, Cisneros J, Gaxiola M, Pérez-Padilla R, Navarro C, Richards T et al (2207) Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern. PLoS ONE 2: e482CrossRefGoogle Scholar
  52. 52.
    Atkinson JJ, Senior RM (2003) Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol 28: 12–24PubMedCrossRefGoogle Scholar
  53. 53.
    Betsuyaku T, Fukuda Y, Parks WC, Shipley JM, Senior RM (2000) Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin. Am J Pathol 157: 525–535PubMedGoogle Scholar
  54. 54.
    Cabrera S, Gaxiola M, Arreola JL, Ramírez R, Jara P, D’Armiento J, Selman M, Pardo A (2007) Overexpression of MMP9 in macrophages attenuates pulmonary fibrosis induced by bleomycin. Int J Biochem Cell Biol 39: 2324–2338PubMedCrossRefGoogle Scholar
  55. 55.
    Yoon HK, Cho HY, Kleeberger SR (2007) Protective role of matrix metalloproteinase-9 in ozone-induced airway inflammation. Environ Health Perspect 115: 1557–1563PubMedCrossRefGoogle Scholar
  56. 56.
    Van den Steen PE, Proost P, Wuyts A, Van Damme J, Opdenakker G (2000) Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-and leaves RANTES and MCP-2 intact. Blood 96: 2673–2681PubMedGoogle Scholar
  57. 57.
    Van Den Steen PE, Wuyts A, Husson SJ, Proost P, Van Damme J, Opdenakker G (2003) Gelatinase B/MMP-9 and neutrophil collagenase/MMP-8 process the chemokines human GCP-2/CXCL6, ENA-78/CXCL5 and mouse GCP-2/LIX and modulate their physiological activities. Eur J Biochem 270: 3739–3749CrossRefGoogle Scholar
  58. 58.
    Manoury B, Nénan S, Guénon I, Lagente V, Boichot E (2007) Influence of early neutrophil depletion on MMPs/TIMP-1 balance in bleomycin-induced lung fibrosis. Int Immunopharmacol 7: 900–911PubMedCrossRefGoogle Scholar
  59. 59.
    Chirco R, Liu XW, Jung KK, Kim HR (2006) Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev 25: 99–113PubMedCrossRefGoogle Scholar
  60. 60.
    Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP (1997) Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74: 111–122PubMedGoogle Scholar
  61. 61.
    Murphy G, Willenbrock F (1995) Tissue inhibitors of matrix metalloendopeptidases. Methods Enzymol 248: 496–510PubMedCrossRefGoogle Scholar
  62. 62.
    García-Alvarez J, Ramirez R, Checa M, Nuttall RK, Sampieri CL, Edwards DR, Selman M, Pardo A (2006) Tissue inhibitor of metalloproteinase-3 is up-regulated by transforming growth factor-beta1 in vitro and expressed in fibroblastic foci in vivo in idiopathic pulmonary fibrosis. Exp Lung Res 32: 201–214PubMedCrossRefGoogle Scholar
  63. 63.
    Jung KK, Liu XW, Chirco R, Fridman R, Kim HR (2006) Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein. EMBO J 25: 3934–3942PubMedCrossRefGoogle Scholar
  64. 64.
    Kolb M, Bonniaud P, Galt T, Sime PJ, Kelly MM, Margetts PJ, Gauldie J (2002) Differences in the fibrogenic response after transfer of active transforming growth factor-beta1 gene to lungs of ‘fibrosisprone’ and ‘fibrosis-resistant’ mouse strains. Am J Respir Cell Mol Biol 27: 141–15PubMedGoogle Scholar
  65. 65.
    Manoury B, Caulet-Maugendre S, Guénon I, Lagente V, Boichot E (2006) TIMP-1 is a key factor of fibrogenic response to bleomycin in mouse lung. Int J Immunopathol Pharmacol 19: 471–487PubMedGoogle Scholar
  66. 66.
    Kim KH, Burkhart K, Chen P, Frevert CW, Randolph-Habecker J, Hackman RC, Soloway PD, Madtes DK (2005) Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice. Am J Respir Cell Mol Biol 33: 271–279PubMedCrossRefGoogle Scholar
  67. 67.
    Van den Steen PE, Van Aelst I, Hvidberg V, Piccard H, Fiten P, Jacobsen C, Moestrup SK, Fry S, Royle L, Wormald MR et al (2006) The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. J Biol Chem 281: 18626–18637PubMedCrossRefGoogle Scholar
  68. 68.
    Fattman CL, Gambelli F, Hoyle GW, Pitt BR, Ortiz LA (2008) Epithelial expression of TIMP1 does not alter sensitivity to bleomycin-induced lung injury in C57BL/6 mice. Am J Physiol Lung Cell Mol Physiol 294: L572–581PubMedCrossRefGoogle Scholar
  69. 69.
    Desmouliere A, Redard M, Darby I, Gabianni G (1995) Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 146: 56–66PubMedGoogle Scholar
  70. 70.
    Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ (1998) Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 102: 538–549PubMedCrossRefGoogle Scholar
  71. 71.
    Murawaki Y, Ikuta Y, Kawasaki H (1999) Clinical usefulness of serum tissue inhibitor of metalloproteinases (TIMP)-2 assay in patients with chronic liver disease in comparison with serum TIMP-1. Clin Chim Acta 281: 109–120PubMedCrossRefGoogle Scholar
  72. 72.
    Hemmann S, Graf J, Roderfeld M, Roeb E (2007) Expression of MMPs and TIMPs in liver fibrosis — a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol 46: 955–975PubMedCrossRefGoogle Scholar
  73. 73.
    Leco KJ, Waterhouse P, Sanchez OH, Gowing KL, Poole AR, Wakeham A, Mak TW, Khokha R (2001) Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3). J Clin Invest 108: 817–829PubMedGoogle Scholar
  74. 74.
    Pottier N, Chupin C, Defamie V, Cardinaud B, Sutherland R, Rios G, Gauthier F, Wolters PJ, Berthiaume Y, Barbry P et al (2007) Relationships between early inflammatory response to bleomycin and sensitivity to lung fibrosis: a role for dipeptidyl-peptidase I and tissue inhibitor of metalloproteinase-3? Am J Respir Crit Care Med 176: 1098–1107PubMedCrossRefGoogle Scholar
  75. 75.
    Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L, Bond M, Baker A, Anand-Apte B (2003) A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med 9: 407–415PubMedCrossRefGoogle Scholar
  76. 76.
    Cosgrove GP, Brown KK, Schiemann WP, Serls AE, Parr JE, Geraci MW, Schwarz MI, Cool CD, Worthen GS (2004) Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis. Am J Respir Crit Care Med 170: 242–251PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Annie Pardo
    • 1
  • Moisés Selman
    • 2
  1. 1.Facultad de Ciencias, Universidad Nacional Autónoma de MéxicoCiudad UniversitariaMéxico DFMéxico
  2. 2.Instituto Nacional de Enfermedades Respiratorias, TlalpanMéxico DFMéxico

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