The role of the transcription factor Sox2 and cytokeratins in the formation and development of the gastroesophageal junction epithelial cell differon

Abstract

The source of the origin of the epithelium of the cardiac part stomach mucosa has been repeatedly discussed in the literature and different variants of the transformation of the epithelium as manifestation of normal anatomical peculiarities of a man and as a result of changing the program of stem cell differentiation, migration of bone marrow cells, transdifferentiation of simple columnar epithelium have been proposed. Probably it is related to difficulties of studying insignificant in size epithelium of the cardiac mucosa itself and establishment of connection of the duodenogastroesophageal reflux with the development of metaplasia in the epithelium of the terminal department of the esophagus mucosa, which resembles its structure in the cardiac part of the stomach. The purpose of the research was to study the expression of the transcription factor Sox2 and the distribution of cytokeratins in the epithelium of the gastroesophageal zone during the stages of the embryonic and fetal periods of ontogenesis. According to the purpose of the research, an immunohistochemical analysis of the epithelial differon of the esophageal-gastric junction (GEJ) was used. The current study was carried out on 169 human embryos and fetuses of gestational age from 4-5 till 38 weeks. It was established that the transcription factor Sox2 is expressed in basal epitheliocytes of GEJ in all terms of observation and plays a major role in the development, differentiation and formation of the epithelial cell lineage of GEJ. The peculiarity of expression of cytokeratin 7 was positive marking in the cytoplasm of spinosum epitheliocytes, despite the negative expression in the basal layer. It showed weak expression in the epitheliocytes of the esophageal part of the GEJ in the embryonic period with an increased reaction in the embryo-fetal period and with subsequent disappearance, starting at 14 weeks in the early fetal period. For the cardiac mucous membrane GEJ was characterized by its moderate expression on all terms of observation. Cytokeratin 8/18 is embryo-fetal for the esophageal part of the esophagus, as it is defined in early periods of embryogenesis and disappears in the late period (28-38 weeks). For the cardiac mucous membrane GEJ was characterized by its moderate expression on all terms of observation. Cytokeratin 14, unlike CK7 and CK8/18, was localized in the cytoplasm and membranes of basal epitheliocytes of the esophageal part of the mucosa from the 17 gestational weeks and was absent in the gastrointestinal part of the GEJ throughout the prenatal period. Thus, our data on the expression of the transcription factor Sox2 and cytokeratins in the GEJ epithelial differon in the prenatal period of ontogenesis will improve the diagnostic accuracy in determining tissue or organ belonging and can be widely used in various GEJ diseases.