Ma Li, Shi Bing, Zheng Qian
Department of Stomatology, Shandong Provincial Hospital affiliated to Shandong University, Jinan.
Department of Cleft Lip and Palate Surgery, West China Stomatological Hospital, Sichuan University.
J Craniofac Surg. 2018 Mar;29(2):260-263. doi: 10.1097/SCS.0000000000004055.
Accumulating studies demonstrated that PAR complex contributed to the establishment and maintenance of cell polarity which was fundamental to many aspects of cell and developmental biology. The purpose of this study was to investigate whether dexamethasone (DEX) could downregulate the PAR complex and disrupt cell polarity in palatal epithelium during palatal fusion in mice. The C57BL/6J mice were selected for the experiment. Pregnant mice in control group and DEX-treated group were injected intraperitoneally with 0.9% sodium chloride 0.1 mL, which contained DEX 6 mg/kg respectively, every day from E10 to E12. The palatal epithelia morphology was observed with hematoxylin and eosin and scanning electron microscopy. Immunofluorescence staining, western blot, and real-time polymerase chain reaction were performed to detect the expression of PAR3/PAR6/aPKC. After being treated with DEX, the palatal shelves showed delayed development and became shorter and smaller. During the process of palatogenesis, PAR3 and PAR6 expressed in the palatal epithelium, and aPKC expressed in both the epithelium and the mesenchyme. Dexamethasone could downregulate the expression levels of PAR3/PAR6/aPKC in both protein and gene level. In conclusions, DEX affected the PAR complex of mouse embryonic palate, and could perturb the PAR complex and the cell polarity of medial edge epithelium cells, and caused the failure of palatal fusion.
越来越多的研究表明,PAR复合物有助于细胞极性的建立和维持,而细胞极性是细胞和发育生物学许多方面的基础。本研究的目的是探讨地塞米松(DEX)是否能下调PAR复合物并破坏小鼠腭融合过程中腭上皮的细胞极性。选择C57BL/6J小鼠进行实验。对照组和DEX处理组的孕鼠从胚胎第10天(E10)至第12天(E12)每天腹腔注射0.1 mL含DEX 6 mg/kg的0.9%氯化钠溶液。用苏木精和伊红染色以及扫描电子显微镜观察腭上皮形态。进行免疫荧光染色、蛋白质印迹法和实时聚合酶链反应以检测PAR3/PAR6/aPKC的表达。经DEX处理后,腭突发育延迟,变得更短更小。在腭发育过程中,PAR3和PAR6在腭上皮中表达,aPKC在上皮和间充质中均有表达。地塞米松可在蛋白质和基因水平下调PAR3/PAR6/aPKC的表达水平。总之,DEX影响小鼠胚胎腭的PAR复合物,可扰乱PAR复合物和内侧边缘上皮细胞的细胞极性,导致腭融合失败。