LKB1调控Peutz-Jeghers综合征错构瘤及肠上皮细胞中的上皮间质转化

发布时间：2018-05-26 17:08

本文选题：LKB + 上皮间质转化　；参考：《南方医科大学学报》2017年08期

【摘要】：目的探讨LKB1在Peutz-Jeghers综合征(PJS)错构瘤及肠上皮细胞中对上皮间质转化(EMT)调控作用。方法采用免疫组化法检测20例PJS错构瘤标本及10例正常肠道组织中LKB1、ecadherin、vimentin蛋白的表达。Masson三色染色法分析胶原纤维沉积。选取NCM460人肠上皮细胞株,慢病毒转染后建立LKB1敲低及空载体稳定表达株。以CCK8实验和transwell迁移实验评价LKB1敲低对细胞增殖、迁移的影响。运用WB、q PCR、免疫荧光检测LKB1敲低后对细胞中EMT相关蛋白ecadherin、vimentin、ncadherin、snail、slug表达的影响。结果与正常肠组织相比,PJS错构瘤中LKB1和ecadherin蛋白表达下降,而vimentin蛋白表达增加。Masson染色提示错构瘤中胶原纤维沉积增多,沉积面积扩大。与空载体组相比,LKB1敲低的NCM460细胞增殖、迁移能力明显增强(P0.01),细胞中ecadherin表达降低,ncadherin、vimentin、snail、slug表达增高。结论LKB1可能通过调控EMT从而影响PJS错构瘤的形态改变及纤维化进程,提示EMT可能成为PJS治疗的新靶点。
[Abstract]:Objective to investigate the regulatory effect of LKB1 on epithelial mesenchymal transformation in hamartoma and intestinal epithelial cells of Peutz-Jeghers syndrome. Methods Immunohistochemical method was used to detect the expression of LKB1 ecadherininvimentin protein in 20 PJS hamartoma specimens and 10 normal intestinal tissues. NCM460 human intestinal epithelial cell line was selected and stable expression strain of LKB1 knockdown and empty vector was established after lentivirus transfection. The effects of low LKB1 knockout on cell proliferation and migration were evaluated by CCK8 assay and transwell migration assay. The effect of LKB1 knockout on the expression of EMT related protein (ecadherin) snailslug in cells was detected by immunofluorescence. Results the expression of LKB1 and ecadherin protein in PJS hamartoma was lower than that in normal intestinal tissue, while the expression of vimentin protein was increased. Masson staining indicated that collagen fiber deposition and deposition area were increased in hamartoma. Compared with the empty vector group, the NCM460 cells with low LKB1 knockout significantly increased their migration ability, and the expression of ecadherin decreased, and the expression of ncadherin vimentinine snailslug increased. Conclusion LKB1 may influence the morphological changes and fibrosis process of PJS hamartoma by regulating EMT, suggesting that EMT may be a new target for PJS therapy.
【作者单位】：南方医科大学南方医院消化内科//广东省胃肠疾病重点实验室;青岛大学附属医院感染科;广东省广州市番禺区人民医院消化内科;
【基金】：国家自然科学基金(81401925) 广东省自然科学基金(2014A030313285)~~
【分类号】：R596.1

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