REGULATION OF COLLAGEN EXPRESSION AND CELL GROWTH IN FIBROPROLIFERATIVE DISEASES

我们的长期目标是阐明正常的伤口愈合过程， 其异常导致纤维化疾病如瘢痕疙瘩， 牙龈增生和牙周病的牙龈纤维化。到 了解这些纤维增生性疾病，其中一些发生在 在黑人群体中异常高的频率，我们建议1）确定 正常人中特定纤维和非纤维胶原类型的水平 和患病的牙龈和皮肤组织中， 从组织;和2）检查各种调节剂的作用， 炎症和伤口愈合对细胞生长和表达的影响 各种类型的胶原蛋白。该项目的具体目标是： 1.评价组织和成纤维细胞从正常牙龈和真皮与 关于I、III、V、XII型胶原蛋白和I型三聚体的表达。 2.将特定目标1中的观察结果扩展至以下组织中的受累组织： 牙龈增生、慢性牙周炎和瘢痕疙瘩患者， 以及从这些组织培养的成纤维细胞。 3.确定炎症和组织的各种介质的影响 修复细胞生长和上述胶原类型的表达。 这些将包括以下介质显示调节生长， 正常组织和纤维化组织中胶原蛋白的合成不同： 氢化可的松，转化生长因子β（TGF β），白细胞介素- 1（IL-1）、佛波酯肿瘤促进剂和前列腺素E2（PGE 2）。 4.确定Ca++通道阻滞剂诱导牙龈炎的作用 增生对成纤维细胞生长及胶原基因表达的影响 在存在和不存在介质的情况下， 炎症。 这些研究可能有助于阐明特定介导物对 在正常和异常伤口愈合期间的生长和胶原蛋白合成， 并确定是否有共同的因素，在病因学 牙龈增生，慢性牙周炎牙龈纤维化 疾病和瘢痕疙瘩。

Our long term goal is to elucidate the normal wound healing process and abnormalities thereof that result in fibrotic diseases such as keloids , gingival hyperplasia and the gingival fibrosis of periodontal disease. To understand these fibroproliferative diseases, several of which occur at unusually high frequency in Black populations, we propose 1) to determine the level of specific fibrillar and nonfibrillar collagen types in normal and diseased gingival and dermal tissue and in fibroblast cultures derived from the tissues; and 2) to examine the effects of various modulators of inflammation and wound healing on cell growth and on the expression of various collagen types. The specific aims of the project are to: 1. Evaluate tissue and fibroblasts from normal gingiva and dermis with respect to expression of collagen types I,III,V,XII and type I trimer. 2. Extend the observations from Specific Aim 1, to involved tissues from patients with gingival hyperplasia, chronic periodontitis, and keloids, and to fibroblasts cultured from these tissues. 3. Determine the effects of various mediators of inflammation and tissue repair on cell growth and on the expression of the above collagen types. These will include the following mediators shown to regulate growth and collagen synthesis differently in normal and fibrotic tissue: hydrocortisone, transforming growth factor beta (TGFbeta), interleukin- 1(IL-1), phorbol ester tumor promotors and prostaglandin E2 (PGE2). 4. Determine the effects of Ca++ channel blockers that induce gingival hyperplasia on cell growth and collagen gene expression in fibroblasts from normal and fibrotic tissue in the presence and absence of mediators of inflammation. These studies may help to elucidate the role of specific mediators on growth and collagen synthesis during normal and abnormal wound healing, and to determine whether there are common elements in the etiology of gingival hyperplasia, the gingival fibrosis of chronic periodontal disease, and keloids.