呼吸系统疾病的分子病理学.pptx

呼吸系统疾病的分子病理学 2015-9-28个人简介张雪,博士、副教授、博士生导师。 浙江大学医学部基础医学院病理与病理生理学系研究领域呼吸系统疾病的分子病理学机制研究； 炎症与损伤在呼吸系统疾病中的作用及其分子机制； 炎症因子及趋化因子的谷胱甘肽化修饰后的功能及其在肺部炎症中的作用。联系方式浙江大学紫金港校区科研楼A310,?0571hangxue@zju.edu.cnOutline呼吸系统的发育和生物学基础常见呼吸系统疾病及其分子病理学机制 感染性疾病 免疫炎症性疾病 遗传性疾病 呼吸系统肿瘤研究方法举例 1.呼吸系统的发育A: 7-8 week embryonic human lungs. The mainstem bronchi have already branched into lobar and segmental bronchi.There are three lobes in the right lung and two in the leftB: lung embryonic day 12 murine lungs. There are four lobes in the right lung and one in the left lung.人与小鼠的肺发育进程对比胚胎期、假腺管期、小管期、囊泡期、肺泡期Branching morphogenesisPulmonary organogenesisAlveolarizationE17-18小鼠肺发育的主要过程Nkx2.1气道上皮细胞的分类及其相关的转录因子In the mouse, large conducting airways (trachea and bronchi) are lined by a pseudostratified epithelium consisting primarily of goblet, basal, Clara (secretory), and ciliated cells. Peripheral conducting airways (bronchioles-acinar ducts, proximal to the alveoli) are lined by a simple columnar epithelium comprised primarily of ciliated and nonciliated cells (Clara cells). Pulmonary neuroendocrine cells (PNEC), some clustered in neuroendocrine bodies (NEBs), are a relatively rare cell type that express serotonin, bombesin, calcitonin gene-related peptide (CGRP), and other neuroendocrine peptides (top panel).转录因子在呼吸道上皮细胞中的分布情况The distribution of transcription factorsvaries among distinct cell types alongthe cephalocaudal axis of the lung. GFI-1,HES, MASH, and RB influence differentiation/growth of neuroendocrine cellsAlveolar type II cells, but not type I cells, express TTF-1, FOXA1/2, C/EBP,NF-1, ERM, and GATA-6. TTF-1, SOX familymembers, p63, FOXJ1, SPDEF, and othertranscription factors vary in concentrationalong the airways where they influence epithelial cell differentiation and gene expression.基因敲除小鼠的表型揭示某些基因在肺发育中的作用The compound null Gli2-/-, Gli3-/- mutant phenotype in which the primitive lung anlage completely fails to arise from the primitive foregut endoderm. Gli2-/- null mutation and Gli