Abstract
Idiopathic pulmonary fibrosis may be described as the debilitating condition of lung where excessive collagen-rich extracellular matrix (ECM) gets deposited. From the chemical and biological properties, it can be assumed that the activities of proteases can degrade matrix. Though, some of the proteases are anti-fibrotic, whereas most of them have profibrotic functions. Proteases perform important functions in a range of biological processes, like tissue repairing, remodeling, and providing immunity. However, the exact mechanism is yet to be known how these enzymes work during fibrosis; i.e., the proteins that the proteases target to perform a specific process and its effect on ECM turnover is still opaque. However, experimental models and clinical studies have identified some crucial steps that could help understanding the disease mechanism and also herald a ground for future therapy.
Abbreviations
- α-SMA:
-
α Α smooth muscle actin
- AHR:
-
Airway hyper reactivity
- ALI:
-
Acute lung injury
- AR:
-
Amphiregulin
- ARDS:
-
Acute respiratory distress syndrome
- BALf:
-
Broncho alveolar lavage fluid
- Cat K:
-
Cathepsin K
- COPD:
-
Chronic obstructive pulmonary disease
- ECM:
-
Extracellular matrix
- EGFR:
-
Epithelial growth factor receptor
- EMT:
-
Epithelial mesenchymal transition
- IPF:
-
Idiopathic pulmonary fibrosis
- IGFBP-3:
-
Insulin growth factor binding protein-3
- MMP:
-
Matrix metalloprotease
- NE:
-
Neutrophil elastase
- PFT:
-
Pulmonary function test
- PTGS2:
-
Prostaglandin G/H synthase 2
- ROC:
-
Receiver operating characteristic curve
- TGF β:
-
Transforming growth factor β
References
Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Kluglich M, de Bios RM (2011) Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 365:1079–1087
Hattori N, Degen JL, Sisson TH, Liu H, Moore BB, Pandrangi RG, Simon RH, Drew AF (2000) Bleomycin-induced pulmonary fibrosis in fibrinogen-null mice. J Clin Invest 106:1341–1350
Swaisgood CM, French EL, Noga C, Simon RH, Ploplis VA (2000) The development of bleomycin-induced pulmonary fibrosis in mice deficient for components of the fibrinolytic system. Am J Pathol 157:177–187
Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ (2006) Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax 61:980–985
Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824
Ley B, Collard HR, King TE (2011) Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 183:431–440
Sisson TH, Matriptase Spagnolo P (2016) Protease-activated receptor 2, and idiopathic pulmonary fibrosis. Further evidence for signaling pathway redundancy in this difficult-to-treat disease? Am J Respir Crit Care Med 193:816–817
Kundu S, Sengupta S, Chatterjee S (2009) Cadmium induces lung inflammation independent of lung cell proliferation: a molecular approach. J Inflamm 6:19. Exp Mol Pathol 92:287–295
Benabid R, Wartelle J, Malleret L (2012) Neutrophil elastase modulates cytokine expression: contribution to host defense against Pseudomonas aeruginosa-induced pneumonia. J Biol Chem 287:34883–34894
Cheronis JC, Repine JE (1993) Proteases, protease inhibitors, and protease-derived peptides: importance in human pathophysiology and therapeutics. Birkhauser, Basel, pp 2–25
Caughey GH (1994) Serine proteinases of mast cell and leukocyte granules: a league of their own. Am J Respir Crit Care Med 150:S138–S142
Shapiro SD (2002) Proteinases in chronic obstructive pulmonary disease. Biochem Soc Trans 30:98–102
Lieberman J (2003) The ABCs of granule-mediated cytotoxicity: new weapon in the arsenal. Nat Rev Immunol 3:361–370
Barnes PJ, Shapiro SD, Pauwels RA (2003) Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 22:672–688
Selman M, Pardo A (2003) The epithelial/fibroblastic pathway in the pathogenesis of idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 29:S93–S97
Bjoraker JA, Ryu JH, Edwin MK (1998) Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 157:199–203
Takishima T, Shimura S (1994) Definition and classification of pulmonary fibrosis. In: Basic and clinical aspects of pulmonary fibrosis. CRC Press, Boca Raton, FL, pp 293–303
Orr CR, Jacobs WF (1926) Pulmonary Fibrosis. Radiology 7:318–325
Hamman L, Rich A (1944) Acute diffuse interstitial fibrosis of the lungs. Bull Johns Hopkins Hosp 74:177–212
Hamman L, Rich AR (1935) Fulminating diffuse interstitial fibrosis of the lungs. Trans Am Clin Climatol Assoc 51:154–163
Schwartz DA, Van Fossen DS, Davis CS (1994) Determinants of progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 149:444–449
King TEJ, Schwarz MI, Brown K (2001) Idiopathic pulmonary fibrosis. Relationship between histopathologic features and mortality. Am J Respir Crit Care Med 164:1025–1032
Scadding JG, Hinson KF (1967) Diffuse fibrosing alveolitis (diffuse interstitial fibrosis of the lungs). Correlation of histology at biopsy with prognosis. Thorax 22:291–304
Crystal RG, Fulmer JD, Roberts WC, Moss ML, Line BR, Reynolds HY (1976) Idiopathic pulmonary fibrosis. Clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects. Ann Intern Med 85:769–788
Hashimoto N, Jin H, Liu T, Chensue SW, Phan SH (2004) Bone marrow-derived progenitor cells in pulmonary fibrosis. J Clin Invest 113:243–252
Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A (1994) Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1:71–81
Kuwana M, Okazaki Y, Kodama H, Izumi K, Yasuoka H, Ogawa Y, Kawakami Ikeda Y (2003) Human circulating CD14+ monocytes as a source of progenitors that exhibit esenchymal cell differentiation. J Leukoc Biol 74:833–845
Postlethwaite AE, Shigemitsu H, Kanangat S (2004) Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol 16:733–738
Willis BC, Liebler JM, Luby-Phelps K (2005) Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1: potential role in idiopathic pulmonary fibrosis. Am J Pathol 166:1321–1332
Coalson JJ (1982) The ultrastructure of human fibrosing alveolitis. Virchows Arch A Pathol Anat Histol 395:181–199
Kawanami O, Ferrans VJ, Crystal RG (1982) Structure of alveolar epithelial cells in patients with fibrotic lung disorders. Lab Invest 46:39–53
Lee Chang-Min, Park Jin Wook, Cho Won-Kyung, Zhou Yang, Han Boram, Yoon Pyoung Oh, Chae Jeiwook, Elias Jack A, Lee Chun Geun (2014) Modifiers of TGF-b1 effector function as novel therapeutic targets of pulmonary fibrosis. Korean J Intern Med 29:281–290
Taooka Y, Maeda A, Hiyama K (1997) Effects of neutrophil elastase inhibitor on bleomycin induced pulmonary fibrosis in mice. Am J Respir Crit Care Med 156:260–265
Lucattelli M, Cavarra E, de Santi MM (2003) Collagen phagocytosis by lung alveolar macrophages in animal models of emphysema. Eur Respir J 22:728–734
Belaaouaj A, McCarthy R, Baumann M (1998) Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med 4:615–618
Lucattelli M, Bartalesi B, Cavarra E et al (2005) Is neutrophil elastase the missing link between emphysema and fibrosis? Evidence from two mouse models. Respir Res 6:83–96
Cabrera S, Maciel M, Herrera I, Nava T, Vergara F, Gaxiola M, López-Otín C, Selman M, Pardo A (2015) Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis. Autophagy 11:670–684
Davis CS, Mendez BM, Flint DV, Pelletiere K, Lowery E, Ramirez L, Love RB, Kovacs EJ, Fisichella PM (2013) Pepsin concentrations are elevated in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis after lung transplantation. J Surg Res 185:e101–e108
Samukawa T, Hamada T, Uto H, Yanagi M, Tsukuya G, Nosaki T, Maeda M, Hirano T, Tsubouchi H, Inoue H (2012) The elevation of serum napsin A in idiopathic pulmonary fibrosis, compared with KL-6, surfactant protein-A and surfactant protein-D. BMC Pulm Med 11(12):55
Fukada 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 disease. Lab Invest 78:687–698
Peters CA, Freeman MR, Fernandez CH, Stephan J, Wiederschain DG, Moses MH (1997) Dysregulated proteolytic balance as the basis of excess extracellular matrix in fibrotic disease. Am J Physiol 272:1960–1965
Yamashita CM, Dolgonos L, Zemans RL, Young SK, Robertson J, Briones N, Suzuki T, Campbell MN, Gauldie J, Radisky DC et al (2011) Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis. Am J Pathol 179:1733–1745
Gadek JE, Kelman JA, Fells G et al (1979) Collagenase in the lower respiratory tract of patients with idiopathic pulmonary fibrosis. N Engl J Med 301:737–742
O’Connor CM, Odlum C, van Breda A, Power C, FitzGerald MX (1988) Collagenase and fibronectin in bronchoalveolar lavage fluid in patients with sarcoidosis. Thorax 43:393–400
Zuo F, Kaminski N, Eugui E, Allard J, Yakhini Z, Ben-Dor A, Lollini L, Morris D, Kim Y, DeLustro B, Sheppard D, Pardo A, Selman M, Heller RA (2002) Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc Natl Acad Sci USA 99:6292–6297
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 111:635–646
McQuibban GA, Gong JH, Wong JP (2002) Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100:1160–1167
Manicone AM, Huizar I, McGuire JK (2009) Matrilysin (Matrix Metalloproteinase-7) regulates anti-inflammatory and antifibrotic pulmonary dendritic cells that express CD103 (alpha (E)beta (7)-integrin). Am J Pathol 175:2319–2331
Garcia-Verdugo I, Descamps D, Chignard M (2010) Lung protease/anti-protease network and modulation of mucus production and surfactant activity. Biochimie 92:1608–1617
García-Prieto E, González-López A, Cabrera S, Astudillo A, Gutiérrez-Fernández A, Fanjul-Fernandez M, Batalla-Solís E, Puente XS, Fueyo A, López-Otín C, Albaiceta GM (2010) Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10. PLoS ONE 5:e13242
Craig VJ, Quintero PA, Fyfe SE, Patel AS, Knolle MD, Kobzik L, Owen CA (2013) Profibrotic activities for matrix metalloproteinase-8 during bleomycin-mediated lung injury. J Immunol 190:4283–4296
Siller-López F, Sandoval A, Salgado S, Salazar A, Bueno M, Garcia J, Vera J, Gálvez J, Hernández I, Ramos M, Aguilar-Cordova E, Armendariz-Borunda J (2004) Treatment with human metalloproteinase-8 gene delivery ameliorates experimental rat liver cirrhosis. Gastroenterology 126:1122–1133
Sun L, Louie MC, Vannella KM, Wilke CA, LeVine AM, Moore BB, Shanley TP (2011) New concepts of IL-10-induced lung fibrosis: fibrocyte recruitment and M2 activation in a CCL2/CCR2 axis. Am J Physiol Lung Cell Mol Physiol 300:L341–L353
Lee WL, Downey GP (2001) Leukocyte elastase: physiological functions and role in acute lung injury. Am J Respir Crit Care Med 164:896–904
Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14:163–176
Betsuyaku T, Fukuda Y, Parks WC, Shipley JM, Senior RM (2000) Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin. Am J Pathol 157:525–535
Cabrera S, Gaxiola M, Arreola JL, Ramírez R, Jara P, D’Armiento J, Richards T, Selman M, Pardo A (2007) Overexpression of MMP9 in macrophages attenuates pulmonary fibrosis induced by bleomycin. Int J Biochem Cell Biol 39:2324–2338
Kaviratne M, Hesse M, Leusink M, Cheever AW, Davies SJ, McKerrow JH, Wakefield LM, Letterio JJ, Wynn TA (2004) IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. J Immunol 173:4020–4029
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 270:3739–3749
Van den Steen PE, Proost P, Wuyts A et al (2000) Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GROalpha and leaves RANTES and MCP-2 intact. Blood 96:2673–2681
Corry DB, Kiss A, Song LZ, Song L, Xu J, Lee SH, Werb Z, Kheradmand F (2004) Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J 18:995
Greenlee KJ, Corry DB, Engler DA, Matsunami RK, Tessier P, Cook RG, Werb Z, Kheradmand F (2006) Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation. J Immunol 177:7312–7321
Kang T, Yi J, Guo A (2001) Subcellular distribution and cytokine-and chemokine regulated secretion of leukolysin/MT6-MMP/MMP-25 in neutrophils. J Biol Chem 276:21960–21968
Matute-Bello G, Wurfel MM, Lee JS, Park DR, Frevert CW, Madtes DK, Shapiro SD, Martin TR (2007) Essential role of MMP-12 in Fas-induced lung fibrosis. Am J Respir Cell Mol Biol 37:210–221
Garbacki N, Di Valentin E, Piette J, Cataldo D, Crahay C, Colige A (2009) Matrix metalloproteinase 12 silencing: a therapeutic approach to treat pathological lung tissue remodeling? Pulm Pharmacol Ther 22:267–278
Madala SK, Pesce JT, Ramalingam TR, Wilson MS, Minnicozzi S, Cheever AW, Thompson RW, Mentink-Kane MM, Wynn TA (2010) Matrix metalloproteinase 12-deficiency augments extracellular matrix degrading metalloproteinases and attenuates IL-13-dependent fibrosis. J Immunol 184:3955–3963
Manoury B, Nenan S, Guenon I, Boichot E, Planquois JM, Bertrand CP, Lagente V (2006) Macrophage metalloelastase (MMP-12) deficiency does not alter bleomycin-induced pulmonary fibrosis in mice. J Inflamm (Lond) 3:2
Lanone S, Zheng T, Zhu Z et al (2002) Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. J Clin Investig 110:463–474
England KA, Price AP, Tram KV, Shapiro SD, Blazar BR, Panoskaltsis-Mortari A (2011) Evidence for early fibrosis and increased airway resistance in bone marrow transplant recipient mice deficient in MMP12. Am J Physiol Lung Cell Mol Physiol 301:L519–L526
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 289:1202–1206
Parks WC, Wilson CL, López-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629
Van Lint P, Libert C (2007) Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol 82:1375–1381
Gill SE, Parks WC (2008) Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol 40:1334–1347
Kolodsick JE, Peters-Golden M, Larios J, Toews GB, Thannickal VJ, Moore BB (2003) Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E. prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation. Am J Respir Cell Mol Biol 29:537–544
White ES, Atrasz RG, Dickie EG, Aronoff DM, Stambolic V, Mak TW, Moore BB, Peters-Golden M (2005) Prostaglandin E(2) inhibits fibroblast migration by E-prostanoid 2 receptor-mediated increase in PTEN activity. Am J Respir Cell Mol Biol 32:135
Huang SK, White ES, Wettlaufer SH, Grifka H, Hogaboam CM, Thannickal VJ, Horowitz JC, Peters-Golden M (2009) Prostaglandin E(2) induces fibroblast apoptosis by modulating multiple survival pathways. FASEB J 23:4317–4326
Lecaille F, Choe Y, Brandt W, Li Z, Craik CS, Brömme D (2002) Selective inhibition of the collagenolytic activity of human cathepsin K by altering its S2 subsite specificity. Biochemistry 41(26):8447–8454
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The authors thank all the laboratory members for their kind support throughout the time and sharing their views and ideas during the scientific discussions. The authors also like to thank Department of Zoology, University of Calcutta, for providing the ideal environment to complete this work.
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Chatterjee, S., Chakraborty, K., Moitra, S., Bhattacharyya, A. (2017). Role of Proteases in Idiopathic Pulmonary Fibrosis. In: Chakraborti, S., Dhalla, N. (eds) Pathophysiological Aspects of Proteases. Springer, Singapore. https://doi.org/10.1007/978-981-10-6141-7_22
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