Mehmet Nizamoglu

36 Chapter 2 Table 3: List of bio-active ECM fragments with (potential) roles in pulmonary fibrosis. (continued) Parent ECM molecule ECM fragment name Molecular mass (kDa) Evidence for alterations in pulmonary fibrosis Mechanism of action Other comments References Collagen type VI Endotrophin (α3 chain) 5.8 Elevated in serum of IPF patients Increases expression of collagen and LOX family genes Regulates TGF-β Promotes fibrosis High levels predict mortality in COPD High levels predict pulmonary fibrosis progression [119-122] Collagen XVIII Endostatin (α1 chain) 21 Increased in serum, plasma and BAL of IPF patients Anti-fibrotic activity in in vitro and in vivo models of fibrosis Regulates angiogenesis, adipogenesis, autophagy. Inhibits activation and activity of MMPs Interacts with integrins and VEGFR2 [123-126] Fibronectin Fibstatin (C-terminal heparin binding domain) 29 Increased in plasma of ILD patients Domains 12-14 (C-terminus) abolishes agonist activity [127] Fragment containing FN III EDA Anastellin Agonist for TLR 4: Domains 9-11 (N-terminus) increases agonist activity of TLR4 [128] Perlecan Endorepellin 85 Parent molecule increased in lung tissue from IPF patients Counteracts endostatin’s regulation of angiogenesis. Interacts with integrins and VEGFR2 [49, 129, 130] Fibulin-1 Fibulin-1C1 Increased in serum and lung tissue of IPF patients Regulates fibrosis and activation of TGFβ Interacts with LTBP-1, collagen and fibronectin [46, 47, 131, 132] BAL: Bronchoalveolar lavage, COPD: Chronic obstructive pulmonary disease, CXCR: CXC chemocine receptor, FN III EDA: Fibronectin extra domain A, ILD: Interstitial lung disease, IPF: Idiopathic pulmonary fibrosis, LOX: Lysyl oxidase, LTBP: Latent TGF-β binding protein, MMP: Matrix metalloproteinase, TGF-β: Transforming growth factor β, TLR: Toll-like receptor, UIP: Usual interstitial pneumonia, VEGFR: Vascular endothelial growth factor receptor

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