title: Osteopontin, a chemotactic protein with cytokine-like properties, is up-regulated in muscle injury caused by Bothrops lanceolatus (fer-de-lance) snake venom.
abstract: Osteopontin (OPN) is a chemotactic, adhesive protein whose receptors include some integrins and matrix proteins known to have role in inflammatory and repair processes. We examined the time course of OPN expression at acute and chronic stages after intramuscular injection of Bothrops lanceolatus venom in rats. Additionally, we examined the expression of CD68 (a marker for phagocytic macrophages) and the myogenic factors, myoD and myogenin. There was a biphasic upregulation of OPN (6-48 h and 3-14 days post-venom), i.e., during acute inflammation and myogenic cell proliferation and differentiation phases. OPN was detected in CD68 + macrophages, fibroblasts, normal and damaged myofibers, myoblasts and myotubes. Myogenin was expressed in the cytoplasm (atypical pattern) and nucleus of myoblasts and myotubes from 18 h to 7 days, after which it was expressed only in nuclei. Macrophage numbers, OPN and myogenin expression were still elevated at 7, 14 and 7 days. At 3 days, when OPN achieved the peak, some clusters of myoblasts were within regions of intense collagen deposition. Fibrosis may represent limitation for repairing processes and may explain the small diameter of regenerated fibers at 21 days post-venom. The expression of OPN in the course of venom-induced damage and regeneration suggests stages-specific mediation role along the whole process.
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), CP 6111, 13081-970 Campinas, SP, Brazil.
authors.forename: Valéria
authors.initials: V
authors.lastname: Barbosa-Souza
authors.forename: Daniel Kiss
authors.initials: DK
authors.lastname: Contin
authors.forename: Waldemar Bonventi
authors.initials: WB
authors.lastname: Filho
authors.forename: Albetiza Lôbo
authors.initials: AL
authors.lastname: de Araújo
authors.forename: Silvia Pierre
authors.initials: SP
authors.lastname: Irazusta
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz-Höfling
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D017837:Bothrops; D049109:Cell Proliferation / Q000187:drug effects; D003435:Crotalid Venoms / Q000633:toxicity*; D007150:Immunohistochemistry; D009132:Muscles / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D053495:Osteopontin / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003435:Crotalid Venoms; D053495:Osteopontin; C067980:CD68 antigen, human; D000097382:CD68 Molecule