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: 6259249
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6259249
• 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 导致瘢痕疙瘩等纤维性疾病的异常， 牙周病的牙龈增生与牙龈纤维化。至 了解这些纤维增生性疾病，其中几种发生在 在黑人群体中异常高的频率，我们建议1)确定 正常人特异性纤维型和非纤维型胶原的水平 和病变的牙龈和真皮组织以及来源于成纤维细胞的培养 从组织中提取；以及2)检测不同调节剂对 炎症和创面愈合对细胞生长和血管内皮生长因子表达的影响 各种类型的胶原蛋白。该项目的具体目标是： 1.对正常牙龈和真皮的组织和成纤维细胞进行评价 关于I、III、V、XII和I型三聚体的表达。 2.将观察范围从特定目标1扩大到所涉及的组织 患有牙龈增生、慢性牙周炎和瘢痕疙瘩的患者， 以及从这些组织培养的成纤维细胞。 3.确定各种炎症介质和组织介质的作用 对细胞生长和上述胶原蛋白表达的修复作用。 这些将包括以下被显示为调节生长和 正常组织和纤维化组织中胶原合成的不同： 氢化可的松、转化生长因子β、白介素2 1(IL-1)、佛波酯类肿瘤促进剂和前列腺素E2(PGE2)。 4.确定钙离子通道阻滞剂对牙龈的影响 细胞增殖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从正常组织和纤维化组织中分离出来 发炎的症状。 这些研究可能有助于阐明特定的介体在 正常和异常伤口愈合过程中的生长和胶原合成， 并确定在病因中是否有共同的因素 牙龈增生与慢性牙周炎的牙周纤维化 疾病和瘢痕疙瘩。