REGULATION OF COLLAGEN EXPRESSION AND CELL GROWTH IN FIBROPROLIFERATIVE DISEASES

纤维增生性疾病中胶原蛋白表达和细胞生长的调节

• 批准号: 6104849
• 负责人: Shirley B. Russell
• 金额: $ 0.27万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104849
• 关键词: calcium channel blockers; cell growth regulation; cellular pathology; collagen; cortisol; dental disorder; fibroblasts; fibrosis; gene expression; gingiva hyperplasia; human subject; human tissue; inflammation; interleukin 1; interleukin 6; keloid skin disorder; oral health; periodontitis; phorbols; prostaglandin E; protein isoforms; tissue /cell culture; transforming growth factors; wound healing

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.

我们的长期目标是阐明正常的伤口愈合过程和 其异常导致纤维化疾病，例如疤痕疙瘩， 牙周病引起的牙龈增生和牙龈纤维化。到 了解这些纤维增生性疾病，其中一些发生在 在黑人群体中出现的频率异常高，我们建议 1) 确定 正常人特定纤维状和非纤维状胶原类型的水平 以及患病的牙龈和真皮组织以及衍生的成纤维细胞培养物 来自组织； 2）检查各种调节剂的影响 炎症和伤口愈合对细胞生长和表达的影响 各种胶原蛋白类型。该项目的具体目标是： 1. 评估正常牙龈和真皮的组织和成纤维细胞 关于 I、III、V、XII 型胶原蛋白和 I 型三聚体的表达。 2. 将观察范围从具体目标 1 扩展到以下组织： 牙龈增生、慢性牙周炎、疤痕疙瘩患者， 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蛋白类型的表达。 这些将包括以下被证明可以调节生长和 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 (TGFbeta)、白细胞介素 1(IL-1)、佛波酯肿瘤启动子和前列腺素 E2 (PGE2)。 4.确定Ca++通道阻滞剂诱导牙龈的作用 增生对成纤维细胞生长和胶原蛋白基因表达的影响 在存在或不存在介质的情况下来自正常组织和纤维化组织 炎症。 这些研究可能有助于阐明特定介质对 正常和异常伤口愈合过程中的生长和胶原蛋白合成， 并确定其病因学中是否存在共同点 牙龈增生、慢性牙周牙龈纤维化 疾病和疤痕疙瘩。