FIBRIN GEL CONTRACTION & MATRIX SYNTHESIS BY FIBROBLASTS

修复创伤或外科手术后的修复和再生过程 伤害是有机体免受其伤害的一种基本保护 环境。因此，皮肤创伤愈合不仅是最多的 重要的研究课题，但由于复杂，也是一个具有挑战性的课题 皮肤的本性。伤口愈合的一般特征已被描述。 (皮科克，E.E.1984)然而，愈合的确切机制仍然存在。 未定义。研究计划的长期目标是了解 创面纤维增生的细胞和生化机制 修理。从这项研究中获得的信息将揭示出重要的 成纤维细胞-纤维蛋白相互作用中必不可少的生物学事件的细节 并可能导致治疗瘢痕疙瘩和增生性瘢痕 其他病理性皮肤病。 在拟议项目的五年期间，研究将集中在 皮肤成纤维细胞与纤维蛋白的相互作用及其对血管内皮生长的影响 利用体外三维纤维蛋白凝胶培养重建基质 系统。将系统研究以下具体目标。 成纤维细胞上纤维蛋白原受体的鉴定和纯化。 我们将研究纤维蛋白与成纤维细胞的结合特性，并使用 用抗体和粘附肽研究细胞的黏附功能 纤维蛋白原基质和纤维蛋白凝胶中的成纤维细胞 化学交联和亲和层析分离 受体。 研究成纤维细胞类型、年龄和密度对成纤维细胞的影响 纤维蛋白凝胶的收缩。我们将培养乳头状和网状结构 真皮成纤维细胞的分离及其与纤维蛋白相互作用的研究 凝胶在凝胶中收缩和降解。 研究转化生长因子-β对纤维蛋白凝胶成纤维细胞收缩的影响。 初步研究表明，转化生长因子-β增强了凝胶的收缩 并在无血清条件下防止纤溶。我们将进一步 探讨其影响纤维蛋白基质收缩的机制 以及成纤维细胞的降解。 纤维蛋白凝胶培养的成纤维细胞合成胶原的研究 转化生长因子-β在此过程中的作用。首先，我们将研究胶原蛋白 由成纤维细胞在纤维蛋白凝胶中合成，并与单层和 胶原蛋白凝胶培养；第二，纤溶对胶原蛋白的影响 合成和参与裂解过程的酶；第三， 转化生长因子-β对胶原合成的影响及其调控研究 黄曲霉毒素对纤维蛋白降解和胶原合成的影响 成纤维细胞。 五、研究瘢痕疙瘩成纤维细胞的行为 纤维蛋白凝胶收缩和胶原生成中的增生性瘢痕 转化生长因子-β在此过程中的作用。我们将使用分离的成纤维细胞 分别来自乳头状真皮和网状真皮 探讨该组织可能的病理机制。 纤维化症。

The process of repair and regeneration following traumatic or surgical injuries represents a fundamental protection of an organism against its environment. Thus, cutaneous wound healing is not only one of the most important research subjects, but also a challenging one due to the complex nature of skin. The general features of wound healing have been described (Peacock, E. E. 1984.), however, the exact mechanisms of healing remain undefined. The long term objective of the research plan is to understand the cellular and biochemical mechanisms underlying fibroplasia in wound repair. The information gained from this study will uncover important details of biological events essential in fibroblast-fibrin interactions and possibly lead to the treatment of keloid and hypertrophic scars and other pathologic skin conditions. During the five years of the proposed project, research will focus on the interactions between skin fibroblasts and fibrin and their influence on matrix remodeling using an in vitro 3-dimensional fibrin gel culture system. The following specific aims will be systematically studied. I. Characterization and purification of fibrinogen receptor on fibroblasts. We will study the binding characteristic of fibrin to fibroblasts, and use antibodies and adhesion peptides to investigate the adhesion function of fibroblasts on fibrinogen substratum and in fibrin gels and use the methods of chemical crosslinking and affinity chromatography to isolate the receptor. I. Study the effect of fibroblast types, age, and density on fibroblast contraction of fibrin gels. We will culture papillary and reticular fibroblasts separately from dermis and study their interactions with fibrin gels in gel contraction and degradation. III. Study the effect of TGF-beta on fibroblast contraction of fibrin gels. A preliminary study has indicated that TGF-beta enhanced gel contraction and prevented fibrinolysis under serum free condition. We will further investigate the mechanism of the effect regarding fibrin matrix contraction and degradation by fibroblasts. IV. Study collagen synthesis by fibroblasts cultured in fibrin gels and the effect of TGF-beta on the process. First, we will study the collagen synthesized by fibroblasts in fibrin gels and compare to monolayer and collagen gel cultures; second, the effect of fibrinolysis on collagen synthesis and the enzyme that involved in the lytic process; and third, the effect of TGF-beta on collagen synthesis and examine its regulatory mechanisms on both fibrin degradation and collagen synthesis by fibroblasts. V. To study the behavior of fibroblasts isolated from keloids and hypertrophic scars in fibrin gel contraction and collagen production and the effect of TGF-beta on the process. We will use fibroblasts isolated from papillary and reticular dermis separately in the studies and investigate the possible pathologic mechanism involved in the tissue fibrosis.