CORNIFIED ENVELOPE PROTEINS & PERMEABILITY BARRIER

角化包膜蛋白

• 批准号: 2842673
• 负责人: Peter M Elias
• 金额: $ 26.7万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2842673
• 关键词: SCID mouse; calcium channel; calcium channel blockers; calcium flux; calcium ion; clinical research; congenital skin disorder; cytoskeletal proteins; gene deletion mutation; genetically modified animals; homeostasis; human subject; intermediate filaments; keratinization; keratinocyte; laboratory mouse; membrane permeability; protein structure function; skin absorption; structural biology; voltage gated channel

Normal keratinocytes undergo differentiation in vitro in a manner regulated by calcium. Cytokines, tumor necrosis factor - alpha (TNF) and interferon- gamma (IFN) (which have receptors on keratinocytes), and the steroid hormone, 1,25 dihydroxy vitamin D3 [1,25(OH)2D], (which is produced by keratinocytes) promote the differentiation of normal keratinocytes, probably through calcium dependent mechanisms. Squamous carcinoma cell lines (SCC lines) show remarkable fidelity in their genotype to normal keratinocytes, but exhibit different degrees of differentiation in vitro. Some SCC lines remain in their proliferative stage of growth and cannot be induced to differentiate by calcium. In this proposal we address the question whether SCC lines respond to the prodifferentiating effect of 1,25(OH)2D, TNF and IFN, and whether the failure of SCC lines to differentiate normally is due to a defect in the calcium dependent intracellular molecular mechanisms by which these agents regulate differentiation.

正常角质形成细胞在体外以一种 由钙调节。 细胞因子，肿瘤坏死因子-α（TNF）和 干扰素-γ（IFN）（其在角质形成细胞上具有受体）， 类固醇激素，1，25二羟基维生素D3 [1，25（OH）2D]，（ 由角质形成细胞产生）促进正常的 角质形成细胞，可能通过钙依赖机制。 鳞状 癌细胞系（SCC系）在其细胞周期中显示出显著的保真度。 基因型正常角质形成细胞，但表现出不同程度的 体外分化。 一些SCC细胞系仍处于增殖状态， 生长阶段，不能被钙诱导分化。 在 本建议我们解决的问题是否SCC线响应 1，25（OH）2D、TNF和IFN的促分化作用，以及 SCC线不能正常区分是由于 钙依赖的细胞内分子机制， 因子调节分化。