Snyder Jessica M, Washington Ida M, Birkland Timothy, Chang Mary Y, Frevert Charles W
Department of Comparative Medicine, University of Washington, Seattle, Washington (JMS, IMW, MYC, CWF)
Center for Lung Biology, University of Washington, Seattle, Washington (TB, MYC, CWF)
J Histochem Cytochem. 2015 Dec;63(12):952-67. doi: 10.1369/0022155415610383. Epub 2015 Sep 18.
Versican, a chondroitin sulfate proteoglycan, is important in embryonic development, and disruption of the versican gene is embryonically lethal in the mouse. Although several studies show that versican is increased in various organs during development, a focused quantitative study on versican expression and distribution during lung and central nervous system development in the mouse has not previously been performed. We tracked changes in versican (Vcan) gene expression and in the accumulation and degradation of versican. Vcan expression and quantitative immunohistochemistry performed from embryonic day (E) 11.5 to E15.5 showed peak Vcan expression at E13.5 in the lungs and brain. Quantitative mRNA analysis and versican immunohistochemistry showed differences in the expression of the versican isoforms in the embryonic lung and head. The expression of Vcan mRNA and accumulation of versican in tissues was complementary. Immunohistochemistry demonstrated co-localization of versican accumulation and degradation, suggesting distinct roles of versican deposition and degradation in embryogenesis. Very little versican mRNA or protein was found in the lungs of 12- to 16-week-old mice but versican accumulation was significantly increased in mice with Pseudomonas aeruginosa lung infection. These data suggest that versican plays an important role in fundamental, overlapping cellular processes in lung development and infection.
多功能蛋白聚糖是一种硫酸软骨素蛋白聚糖,在胚胎发育中起重要作用,多功能蛋白聚糖基因的破坏在小鼠胚胎期是致死性的。尽管多项研究表明多功能蛋白聚糖在发育过程中在各个器官中表达增加,但此前尚未对小鼠肺和中枢神经系统发育过程中多功能蛋白聚糖的表达和分布进行过针对性的定量研究。我们追踪了多功能蛋白聚糖(Vcan)基因表达以及多功能蛋白聚糖的积累和降解变化。从胚胎第(E)11.5天到E15.5天进行的Vcan表达和定量免疫组织化学显示,肺和脑中Vcan在E13.5天表达达到峰值。定量mRNA分析和多功能蛋白聚糖免疫组织化学显示,胚胎肺和头部中多功能蛋白聚糖同工型的表达存在差异。Vcan mRNA的表达与组织中多功能蛋白聚糖的积累是互补的。免疫组织化学证明了多功能蛋白聚糖积累和降解的共定位,表明多功能蛋白聚糖沉积和降解在胚胎发生中具有不同作用。在12至16周龄小鼠的肺中发现极少的多功能蛋白聚糖mRNA或蛋白质,但铜绿假单胞菌肺部感染小鼠中多功能蛋白聚糖的积累显著增加。这些数据表明,多功能蛋白聚糖在肺发育和感染的基本重叠细胞过程中起重要作用。