Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdiffe

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:lymoso
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK / STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyzes, based on expression of These 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK / STAT signaling pathway impeded the morphological transdifferentiatio n of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK / STAT signaling may be critical in the early stages of transdifferentiation
其他文献
婚姻中没有完全的平等,只有满足各自需求后的平衡。我的婚姻不平等“要么平等,要么离婚!”云珊坐在诊室里,声声控诉。她的老公立强坐在不远处的沙发上,一言不发。看到立强的
黑蒙性痴呆(Tay-Sachs Disease,TSD)是鞘脂贮积症中较常见的一种。为常染色体隐性遗传性疾病,可通过对高危群体筛查杂合子控制患儿出生的遗传性疾病。现将我们经酶活性测定
多种维生素及微量元素缺乏能引起贫血。虽然营养性贫血最常见的病因是缺铁,其它营养物质缺乏,如维生素 A、维生素 C、维生素 E、维生素 B_6、维生素 B_2、叶酸、维生素 B_(1
磷酸肌酸激酶(creatine phosphokina-se,CPK)及其同功酶活性测定,对于心肌、骨骼肌和中枢神经系统损伤的诊断有一定意义。近年来国外对CPK同功酶活性测定及其在新生儿临床的
“小团体学习”是在教师的指导下,依据学生体能、技能、个性特征为原则,自愿组合而成的一种相互配合、相互帮助、相互激励、相互竞争的教学形式,以更好地实现学生在教学中的主体
高中地理以可持续发展理论为核心,探讨人类与自然环境、社会发展的关系;注重与实际相结合,要求学生在梳理、分析事实的基础上,逐步学会运用基本的地理原理探究地理过程、地理
甲状旁腺功能减低(hypoparathyroid-ism,HP)为甲状旁腺激素(PTH)分泌减低或周围靶组织对PTH抵抗所引起的一组临床疾病,主要表现为神经、肌肉兴奋性增高和低血钙、高血磷。P
报告1976—1985年收治的68例结脑病人,其中94.5%就诊时病情尚属早期,但患者从开始发病至确诊时间平均达30天之久。由于未能及时诊断,至确诊时病情尚在早期者仅占36.7%。简要
1.做员工的不能与老板太贴心  面对金兵的欺压凌辱,岳飞主战,以保家卫国,这实乃天经地义的事情。秦桧主和,本来就是逆势而上,难得人心。就是有老板赵构的支持,也是冒天下之大不韪。可秦桧仗着有老板的支持,昧着良心,硬着头皮,不惜搭上身家性命,愣是以“莫须有”的罪名把岳飞等人加害至死,结果却是替老板世世代代背黑锅,永久钉在历史的耻辱柱上。  秦桧后代就有人因为不肖有这么个祖宗而改姓徐或他姓的。清朝乾隆年