32 Chapter 2 Table 2: Different types of MMPs, their origins, involvement in lung fibrosis and possible mechanisms of action. Substrates for cleavage sourced primarily from [62]. (continued) MMP Source in vivo Localization in lung tissue Profile in lung fibrosis Substrates for Cleavage Possible mechanism of action References MMP15 MT2-MMP AECs and endothelial cells AECs ↑ gene and protein in lung tissue from IPF ECM substrates Fn; tenascin; nidogen; aggrecan; perlecan; Ln ProMMP-2; tissue transglutaminase Not known as yet [70] MMP16 MT3-MMP AECs and fibroblasts AECs and fibroblasts in fibroblastic foci ↑ gene and protein in lung tissue from IPF ECM substrates Collagen type III; Fn; gelatin Non-ECM substrates ProMMP-2; tissue transglutaminase Not known as yet [70] MMP19 Monocytes, macrophages, fibroblasts, and endothelial cells Hyperplastic AECs overlying fibrotic areas ↑ gene in lung tissue from IPF ECM substrates Collagen type IV; gelatin; Fn; tenascin; aggrecan; COMP; Ln; nidogen Non-ECM substrates IGFBP-3 Stimulates epithelial cell wound healing and migration Promotes fibroblast migration, proliferation and ECM component synthesis [93] MMP28 Epilysin bronchial and AECs Bronchial and AECs ↑ in serum from IPF ↑ gene and protein in lung tissue from IPF ECM substrates Unknown Non-ECM substrates Casein Promoting M2 macrophage programming [64, 94, 95] AEC – alveolar epithelial cells; TGF – transforming growth factor; α2-M, α2-macroglobulin; α1-PI, α1-proteinase inhibitor; COMP, cartilage oligomeric matrix protein; CTGF, connective tissue growth factor; Fas-L, Fas ligand; FGF, fibroblast growth factor; Fn, fibronectin; HB-EGF, heparin-binding epidermal growth factor like growth factor; IGFBP, insulin-like growth factor binding protein; ICAM-1, inter-cellular adhesion molecule 1; Kit-L, kit ligand; Ln, laminin; MCP-3, monocyte chemotactic protein-3; MMP, matrix metalloproteinases; MT-MMP, membrane-type MMP; PG, proteoglycan; proIL-1β, pro interleukin-1β ; Pro, proteinase type; proTNF-α, pro tumor necrosis factor-α; proTGF-β, pro transforming growth factor β; ProMMP, latent MMP; RASI-1, rheumatoid arthritis synovium inflamed-1; RANKL, receptor activator for nuclear factor κB ligand; uPA, urokinase plasminogen activator
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