Flanagan Dustin J, Barker Nick, Nowell Cameron, Clevers Hans, Ernst Matthias, Phesse Toby J, Vincan Elizabeth
University of Melbourne and Victorian Infectious Diseases Reference Laboratory, Doherty Institute of Infection and Immunity, Melbourne, Victoria 3000, Australia.
Institute of Medical Biology, Singapore 138648, Singapore.
Dis Model Mech. 2017 Aug 1;10(8):971-980. doi: 10.1242/dmm.029876. Epub 2017 Jun 9.
The gastric epithelium consists of tubular glandular units, each containing several differentiated cell types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation of signalling pathways that regulate homeostasis of the diseased organ. Therefore, it is important to understand the biology of how normal conditions are maintained in a tissue to help inform the mechanisms driving disease in that same tissue, and to identify potential points of therapeutic intervention. Wnt signalling regulates several cell functions, including proliferation, differentiation and migration, and plays a crucial role during homeostasis of several tissues, including the intestinal epithelium. Wnt3a is required in the culture medium of gastric organoids, suggesting it is also important for the homeostasis of the gastric epithelium, but this has not been investigated Here, we show that the Wnt receptor frizzled 7 (Fzd7), which is required for the homeostasis of the intestine, is expressed in the gastric epithelium and is required for gastric organoid growth. Gastric-specific loss of in the adult gastric epithelium of mice is deleterious and triggers rapid epithelial repopulation, which we believe is the first observation of this novel function for this tissue. Taken together, these data provide functional evidence of a crucial role for Wnt signalling, via the Fzd7 receptor, during homeostasis of the gastric epithelium.
胃上皮由管状腺单位组成，每个腺单位包含几种分化的细胞类型以及干细胞群体，这些干细胞使胃能够分泌其功能所需的酸、黏液和各种消化酶。关于胃上皮稳态需要哪些细胞信号通路，我们知之甚少。许多疾病，如癌症，是由于调节患病器官稳态的信号通路失调所致。因此，了解组织中正常状态是如何维持的生物学机制，有助于揭示同一组织中疾病发生的机制，并确定潜在的治疗干预点，这一点很重要。Wnt信号传导调节多种细胞功能，包括增殖、分化和迁移，并且在包括肠上皮在内的多种组织的稳态过程中发挥关键作用。胃类器官培养基中需要Wnt3a，这表明它对胃上皮的稳态也很重要，但尚未对此进行研究。在这里，我们表明，肠道稳态所需的Wnt受体卷曲蛋白7（Fzd7）在胃上皮中表达，并且是胃类器官生长所必需的。在成年小鼠胃上皮中特异性缺失会产生有害影响，并触发上皮细胞的快速重新增殖，我们认为这是该组织这种新功能的首次观察结果。综上所述，这些数据提供了功能性证据，证明Wnt信号通过Fzd7受体在胃上皮稳态过程中发挥关键作用。
