35 The multi-faceted extracellular matrix: unlocking its secrets for understanding the perpetuation of lung fibrosis Table 3: List of bio-active ECM fragments with (potential) roles in pulmonary fibrosis. Parent ECM molecule ECM fragment name Molecular mass (kDa) Evidence for alterations in pulmonary fibrosis Mechanism of action Other comments References Collagen type I Proline-glycine-proline (PGP) (can also be found in Collagen III & IV) 0.269 Not detectable in BAL of IPF patients Administration of PGP to bleomycin challenged mice is protective from development of fibrosis Enhances MMP9 and neutrophil elastase secretion Chemoattractant for leukocytes Promotes repair of epithelial cells, and neo-angiogenesis Engages CXCR1/2 [109-111] Collagen type I α1 Product from cleavage between amino acid positions 1158/1159 Promotes ECM deposition, fibroblast migration [112] Collagen type IV Arresten (α1 chain) 26 Increased in serum of IPF patients. Increased fragment from collagen IV released after MMP12 degradation in IPF Higher levels related to mortality in ILD. Tumstatin and Lamstatin absent in lung tissues of patients with UIP but present in controls Inhibits angiogenesis Turnover is predictive of mortality in COPD [90, 113-118] Canstatin (α2 chain) 24 Promotes fibrosis, MMP2 expression Inhibits lung fibroblast migration, myofibroblast contraction Tumstatin (α3 chain) 27 Inhibits fibroblast proliferation & migration and angiogenesis Tetrastatin (α4 chain) 25 20 AA Inhibits tumurogenesis (probably via inhibiting angiogenesis) Lamstatin / Pentastatin (α5 chain) 25 2.45 Inhibits lymphangiogenesis Inhibits tumorigenesis (probably via inhibiting angiogenesis) Hexastatin (α6 chain) 25 Inhibits migration and survival of endothelial cells 2
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