REGULATION OF DIFFERENTIATION OF TRACHEOBRONCHIAL EPITHELIAL CELLS

气管支气管上皮细胞分化的调控

• 批准号: 3855887
• 负责人: A M JETTEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3855887
• 关键词: biological signal transduction; bronchus; cell cycle; cell differentiation; cell growth regulation; cell population study; cell transformation; cell type; gene expression; genetic regulation; human tissue; messenger RNA; molecular cloning; protein glutamine gamma glutamyltransferase; receptor; respiratory epithelium; retinoate; retinoid binding proteins; tissue /cell culture; trachea; transforming growth factors

The focus of the research in the Cell Biology Section is to understand the mechanisms that regulate the differentiation of tracheobronchial and epidermal epithelial cells and in particular the role that retinoids play in this process. Several factors, including phorbol esters and interferon gamma (IF-gamma) have been identified that control irreversible growth arrest, the first stage in the process o squamous differentiation. In the next stage, a variety of biological, biochemical and molecular changes are induced which determine the squamous-differentiated phenotype. Several squamous cell-specific mRNAs were identified, cloned and sequenced. These include transglutaminase type 1, relaxin and several genes with unknown function, such as SQ37 and CL20. SQ37 appeared to belong to family of at least four highly homologous genes which encode proteins containing 7-12 repeats of eight amino acids. These proteins may fulfill a structural role in the cell. The induction of the squamous phenotype by IF-gamma is antagonized by transforming growth factor beta suggesting an interaction between their signal transduction pathways. Retinoids are important regulators of differentiation of these cells in vivo as well in vitro. Retinoids determine whether tracheobronchial epithelial cells undergo squamous or mucociliary differentiation. The induction of the squamous markers is suppressed by retinoids at the protein as well as mRNA level. The action of retinoids appears to be mediated by the nuclear retinoic acid receptors RAR-alpha, RAR-beta and RAR-gamma. It was proposed that the expression of RARO is a prerequisite for the induction of mucociliary differentiation. Altered expression of RARs may play a role in the process of carcinogenesis in the lung.

细胞生物学部分的研究重点是了解细胞的生物学特性。 调节气管支气管和 表皮上皮细胞，特别是类维生素A在 在这个过程中。 几个因素，包括佛波酯和干扰素 γ-干扰素（IF-γ）已被确定为控制不可逆生长 停止，鳞状分化过程的第一阶段。 在 下一阶段，各种生物、生物化学和分子变化 诱导决定鳞状细胞分化表型。 几 鉴定、克隆和测序鳞状细胞特异性mRNA。 这些 包括1型转氨酶、松弛素和几种未知基因 函数，如SQ 37和CL 20。 SQ 37似乎属于在 至少4个高度同源的基因，编码含有7-12个 八个氨基酸的重复序列。 这些蛋白质可能发挥结构性作用 在细胞中。 IFN-γ对鳞状细胞表型的诱导作用是 被转化生长因子β拮抗，表明相互作用 在它们的信号转导通路之间。 维甲酸很重要 调节这些细胞在体内以及体外的分化。 类维生素A决定气管支气管上皮细胞是否经历 鳞状或粘液纤毛分化。 鳞状细胞癌的诱导 类维生素A在蛋白质和mRNA水平上抑制这些标记物。 类维生素A的作用似乎是由核视黄酸介导的 受体RAR-α、RAR-β和RAR-γ。 有人建议 RARO的表达是诱导粘膜纤毛的先决条件。 分化 RAR的表达改变可能在这一过程中发挥作用 肺癌的发生。