Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), CP 6111, 13081-970 Campinas, SP, Brazil.
Toxicon. 2011 Oct;58(5):398-409. doi: 10.1016/j.toxicon.2011.07.011. Epub 2011 Aug 5.
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.
骨桥蛋白 (OPN) 是一种趋化性、黏附性蛋白,其受体包括一些整合素和基质蛋白,这些蛋白在炎症和修复过程中具有作用。我们检测了巴西矛头蝮蛇毒液肌内注射后急性和慢性阶段 OPN 表达的时间进程。此外,我们还检测了 CD68(吞噬性巨噬细胞的标志物)和肌生成因子 myoD 和 myogenin 的表达。OPN 呈双相上调(6-48 小时和 3-14 天),即在急性炎症和肌生成细胞增殖和分化阶段。OPN 存在于 CD68+巨噬细胞、成纤维细胞、正常和受损的肌纤维、成肌细胞和肌管中。Myogenin 在 18 小时至 7 天的成肌细胞和肌管的细胞质(非典型模式)和核中表达,之后仅在核中表达。7 天、14 天和 7 天时,巨噬细胞数量、OPN 和 myogenin 表达仍升高。在 3 天时,当 OPN 达到峰值时,一些成肌细胞簇位于强烈的胶原沉积区域内。纤维化可能代表修复过程的限制,这可以解释毒液注射后 21 天再生纤维的直径较小。OPN 在毒液诱导的损伤和再生过程中的表达表明,它在整个过程中具有阶段特异性的介导作用。