title: Role of endostatin in fibroproliferative disorders.-as a candidate for anti-fibrosis therapy-.
abstract: There are no effective treatments for fibrosis, an out-of-control wound-healing process in which excessive deposition of extracellular matrix (ECM) such as collagen, resulting in significant morbidity and mortality. Endostatin is a natural proteolytic fragment of collagen XVIII, which is known to possess potent antiangiogenic activity. Many clinical trials of endostatin have been conducted for anti-cancer therapy. In addition to antiangiogenic effects, recent studies have revealed that endostatin may suppress aberrant tissue remodeling and scarring. Neutralization of endogenous endostatin in rat myocardial infarction (MI) model worsened the outcomes of MI, indicating that endostatin may have protective role against left ventricular remodeling and heart failure after MI. Recently, we also reported inhibitory effects of peptides derived from endostatin on fibrosis. A peptide derived from the C-terminus of endostatin suppressed ECM production in fibroblasts in the presence of transforming growth factor-β (TGF-β), prevented TGF-β-induced dermal fibrosis ex vivo in human skin, and ameliorated skin and pulmonary fibrosis induced by bleomycin in vivo. The antifibrotic capacity was accompanied by reduced cell apoptosis and lower levels of lysyl oxidase and early growth response gene-1. Endostation may have the therapeutic potential for inhibiting fibrosis.
authors.affiliation: Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Carol A
authors.initials: CA
authors.lastname: Feghali-Bostwick
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000009:adverse effects; D002921:Cicatrix / Q000517:prevention & control; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D043169:Endostatins / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D051381:Rats; D012595:Scleroderma, Systemic / Q000188:drug therapy*; D012867:Skin / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D051766:Early Growth Response Protein 1; D043169:Endostatins; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D008249:Protein-Lysine 6-Oxidase