Ali Irshad, Rafiee Parvaneh, Zheng Yue, Johnson Christopher, Banerjee Banani, Haasler George, Jacob Howard, Shaker Reza
Division of Gastroenterology and Hepatology, MCW Dysphagia Institute, Digestive Disease Center, Medical Collegeof Wisconsin, Milwaukee, WI 53226, USA.
J Clin Gastroenterol. 2009 Apr;43(4):327-37. doi: 10.1097/mcg.0b013e31816256ff.
The molecular mechanisms governing the biology and pathobiology of esophageal squamous mucosa in health and disease are not completely understood. Earlier genome-wide expression study of normal-looking esophageal squamous mucosa has shown differential expression of the Wingless-type MMTV integration site family (Wnt) modulators Dickkopf (Dkk) homologs among healthy individuals and patients with reflux esophagitis and Barrett metaplasia suggesting that the Wnt pathway may be involved in esophageal mucosal biology.
Seven full-thickness human donor esophagi were cryosectioned for immunohistochemical analysis, and lamina propria (LP), basal (BC), intermediate (IC), and superficial (SC) cells were also dissected by laser-capture microdissection for real-time polymerase chain reaction.
Wnt1, 2b, and 3a were expressed primarily in BC, Wnt3, and 5b in LP, and Wnt5a in IC. Frizzled 1, low-density lipoprotein receptor-related protein 6, secreted frizzled-related protein 1, T-cell-specific transcription factor 3, and dishevelled 3 were expressed highest in LP decreasing precipitously medially toward SC. Dkk1 predominantly expressed in SC was more than 100-folds greater than other layers (P<0.001). Dkk4 was expressed primarily in SC but Dkk3 was opposite with greatest expression in LP. Immunohistochemical analysis showed Wnt1 and 3a in BC, Wnt5a in IC and SC, Dkk1 predominantly in SC, Dkk4 in SC and IC, and Dkk3 and SFRP1 in LP and BC
健康和疾病状态下食管鳞状黏膜生物学及病理生物学的分子机制尚未完全明确。早期对外观正常的食管鳞状黏膜进行的全基因组表达研究显示，在健康个体、反流性食管炎患者和巴雷特化生患者中，无翅型MMTV整合位点家族（Wnt）调节剂Dickkopf（Dkk）同源物存在差异表达，提示Wnt信号通路可能参与食管黏膜生物学过程。
对7例人供体食管全层进行冷冻切片以进行免疫组织化学分析，同时通过激光捕获显微切割技术分离固有层（LP）、基底细胞层（BC）、中间细胞层（IC）和表层细胞层（SC），用于实时聚合酶链反应。
Wnt1、2b和3a主要在BC中表达，Wnt3和5b在LP中表达，Wnt5a在IC中表达。卷曲蛋白1、低密度脂蛋白受体相关蛋白6、分泌型卷曲相关蛋白1、T细胞特异性转录因子3和散乱蛋白3在LP中表达最高，向内侧的SC急剧下降。主要在SC中表达的Dkk1比其他层高100多倍（P<0.001）。Dkk4主要在SC中表达，但Dkk3相反，在LP中表达最高。免疫组织化学分析显示，Wnt1和3a在BC中表达，Wnt5a在IC和SC中表达，Dkk1主要在SC中表达，Dkk
