Matrix Metalloproteinases in Emphysema

Overview

Journal Matrix Biol

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2018 Feb 7

PMID 29406250

Citations 54

Authors

Sina A Gharib

Anne M Manicone

William C Parks

Affiliations

Soon will be listed here.

Abstract

Several studies have implicated a causative role for specific matrix metalloproteinases (MMPs) in the development and progression of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) and its severe sequela, emphysema. However, the precise function of any given MMP in emphysema remains an unanswered question. Emphysema results from the degradation of alveolar elastin - among other possible mechanisms - a process that is often thought to be caused by elastolytic proteinases made by macrophages. In this article, we discuss the data suggesting, supporting, or refuting causative roles of macrophage-derived MMPs, with a focus on MMPs-7, -9, -10, -12, and 28, in both the human disease and mouse models of emphysema. Findings from experimental models suggest that some MMPs, such as MMP-12, may directly breakdown elastin, whereas others, particularly MMP-10 and MMP-28, promote the development of emphysema by influencing the proteolytic and inflammatory activities of macrophages.

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References

Shi G, Munger J, Meara J, Rich D, Chapman H . Molecular cloning and expression of human alveolar macrophage cathepsin S, an elastinolytic cysteine protease. J Biol Chem. 1992; 267(11):7258-62. View

Senior R, Griffin G, Mecham R . Chemotactic responses of fibroblasts to tropoelastin and elastin-derived peptides. J Clin Invest. 1982; 70(3):614-8. PMC: 370263. DOI: 10.1172/jci110654. View

Illman S, Keski-Oja J, Parks W, Lohi J . The mouse matrix metalloproteinase, epilysin (MMP-28), is alternatively spliced and processed by a furin-like proprotein convertase. Biochem J. 2003; 375(Pt 1):191-7. PMC: 1223653. DOI: 10.1042/BJ20030497. View

Atkinson J, Holmbeck K, Yamada S, Birkedal-Hansen H, Parks W, Senior R . Membrane-type 1 matrix metalloproteinase is required for normal alveolar development. Dev Dyn. 2005; 232(4):1079-90. DOI: 10.1002/dvdy.20267. View

Mecham R, Broekelmann T, Fliszar C, Shapiro S, Welgus H, Senior R . Elastin degradation by matrix metalloproteinases. Cleavage site specificity and mechanisms of elastolysis. J Biol Chem. 1997; 272(29):18071-6. DOI: 10.1074/jbc.272.29.18071. View

Manicone A, Gharib S, Gong K, Eddy W, Long M, Frevert C . Matrix Metalloproteinase-28 Is a Key Contributor to Emphysema Pathogenesis. Am J Pathol. 2017; 187(6):1288-1300. PMC: 5455063. DOI: 10.1016/j.ajpath.2017.02.008. View

Leco K, Waterhouse P, Sanchez O, Gowing K, Poole A, Wakeham A . Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3). J Clin Invest. 2001; 108(6):817-29. PMC: 200926. DOI: 10.1172/JCI12067. View

Atkinson J, Senior R . Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol. 2002; 28(1):12-24. DOI: 10.1165/rcmb.2002-0166TR. View

DArmiento J, Dalal S, Okada Y, Berg R, Chada K . Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell. 1992; 71(6):955-61. DOI: 10.1016/0092-8674(92)90391-o. View

10.

Russell R, Thorley A, Culpitt S, Dodd S, Donnelly L, Demattos C . Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases. Am J Physiol Lung Cell Mol Physiol. 2002; 283(4):L867-73. DOI: 10.1152/ajplung.00020.2002. View

11.

Goren I, Allmann N, Yogev N, Schurmann C, Linke A, Holdener M . A transgenic mouse model of inducible macrophage depletion: effects of diphtheria toxin-driven lysozyme M-specific cell lineage ablation on wound inflammatory, angiogenic, and contractive processes. Am J Pathol. 2009; 175(1):132-47. PMC: 2708801. DOI: 10.2353/ajpath.2009.081002. View

12.

Barnes P, Shapiro S, Pauwels R . Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003; 22(4):672-88. DOI: 10.1183/09031936.03.00040703. View

13.

Koller F, Dozier E, Nam K, Swee M, Birkland T, Parks W . Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia. Lab Invest. 2012; 92(12):1749-59. PMC: 3510327. DOI: 10.1038/labinvest.2012.141. View

14.

Giannandrea M, Parks W . Diverse functions of matrix metalloproteinases during fibrosis. Dis Model Mech. 2014; 7(2):193-203. PMC: 3917240. DOI: 10.1242/dmm.012062. View

15.

Dehrmann F, Coetzer T, Pike R, Dennison C . Mature cathepsin L is substantially active in the ionic milieu of the extracellular medium. Arch Biochem Biophys. 1995; 324(1):93-8. DOI: 10.1006/abbi.1995.9924. View

16.

Finkelstein R, Fraser R, Ghezzo H, Cosio M . Alveolar inflammation and its relation to emphysema in smokers. Am J Respir Crit Care Med. 1995; 152(5 Pt 1):1666-72. DOI: 10.1164/ajrccm.152.5.7582312. View

17.

Parks W . Who are the proteolytic culprits in vascular disease?. J Clin Invest. 1999; 104(9):1167-8. PMC: 409834. DOI: 10.1172/JCI8642. View

18.

Pillai S, Ge D, Zhu G, Kong X, Shianna K, Need A . A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 2009; 5(3):e1000421. PMC: 2650282. DOI: 10.1371/journal.pgen.1000421. View

19.

Bergers G, Brekken R, McMahon G, Vu T, Itoh T, Tamaki K . Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000; 2(10):737-44. PMC: 2852586. DOI: 10.1038/35036374. View

20.

Foronjy R, Nkyimbeng T, Wallace A, Thankachen J, Okada Y, Lemaitre V . Transgenic expression of matrix metalloproteinase-9 causes adult-onset emphysema in mice associated with the loss of alveolar elastin. Am J Physiol Lung Cell Mol Physiol. 2008; 294(6):L1149-57. DOI: 10.1152/ajplung.00481.2007. View