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


  • T.O. Rekun Vinnytsya National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • S.V. Vernygorodskyi Vinnytsya National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • T.M. Kyselova Vinnytsya National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • O.V. Tataryna Vinnytsya National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • O.L. Cherepakha Vinnytsya National Pirogov Memorial Medical University, Vinnytsya, Ukraine
Keywords: gastroesophageal junction, immunohistochemical analysis, Sox2 transcription factor, cytokeratins, prenatal ontogenesis

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.

References

[1] Ahmed, Y. A., El-Hafez, A. A. E., & Zayed, A. E. (2016). Histological and Histochemical Studies on the Esophagus, Stomach and Small Intestines of Vara-nus niloticus. arXiv preprint arXiv: 1610.01717.

[2] Avtandilov, G. G. (2007). Basics of pathoanatomical practice. Manual (third edition amended). M.: Russian Medical Academy of Postgraduate Education.

[3] Chen, X., Qin, R., Liu, B., Ma, Y., Su, Y., Yang, C. S., ... & Shaheen, N. J. (2008). Multilayered epithelium in a rat model and human Barrett’s esophagus: similar expression patterns of transcription factors and differentiation markers. BMC gastroenterology, 8(1), 1. doi: 10.1186/1471-230X-8-1.

[4] Danilov, R. K. & Borovaya, T. G. (2003). General and medical embryology. SPb.: SpecLit. ISBN: 5-299-00208-4

[5] De Hertogh, G., Van Eyken, P., Ectors, N., & Geboes, K. (2005). On the origin of cardiac mucosa: A histological and immunohistoc-hemical study of cytokeratin expression patterns in the developing esophagogastric junction region and stomach. World journal of gastroenterology: WJG, 11(29), 4490. doi: 10.3748/wjg.v11.i29.4490.

[6] DeWard, A. D., Cramer, J., & Lagasse, E. (2014). Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell reports, 9(2), 701-711.

[7] Günther, C., Neumann, H., & Vieth, M. (2014). Esophageal epithelial resistance. Dig Dis, 32, 6-10.

[8] Jacobs, I. J., Ku, W. Y., & Que, J. (2012). Genetic and cellular mechanisms regulating anterior foregut and esophageal development. Developmental biology, 369(1), 54-64.

[9] Jazii, F. R. (ed.) (2012). Esophageal Cancer: Cell and Molecular Biology, Biomarkers, Nutrition and Treatment. Intech. P. ISBN: 978-953-51-0223-6

[10] Kalabis, J., Oyama, K., Okawa, T., Nakagawa, H., Michaylira, C. Z., Stairs, D. B., ... & Rustgi, A. K. (2008). A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. The Journal of clinical investigation, 118(12), 3860-3869.

[11] Kulinichenko, V. L., Mishalov, V. D., Tchaikovsky, Yu. B., Pustovit, S. V., & Voichenko, V. V. (2007). Compliance with ethical and legislative norms and requirements in the course of scientific morphological research. Morphology, 1(4), 134-135.

[12] Mazurin, A. B. & Vorontsov, A. B. (2009). Propedeutics of childhood diseases. Foliant, Russia. ISBN: 978-5-93929-184-2

[13] McKeon, F. (2004). p63 and the epithelial stem cell: more than status quo? Genes & development, 18(5), 465-469.

[14] Mishalov, V. D., Voychenko, V. V., Malysheva, T. A., Dibrova, V. A., Kuzik, P. V., & Yurchenko, V. T. (2018). The procedure for the extraction and use of biological objects from dead persons whose bodies are subject to forensic examination and pathologoanatomical research, for scientific purposes. Special edition of the newspaper “Osvita Ukrainy”, 3-13.

[15] Namiot, Z., Sarosiek, J., Marcinkiewicz, M., Meade, C., & Edmunds Richard, W. (1994). McCallum Declined human esophageal mucin secretion in patients with severe reflux esophagiti. Digestive Diseases and Sciences December, 39(12), 2523-2529.

[16] Özefagus, ve Mide Gelişimi. (2017). Development of the esophagus and stomach. Bezmialem Science, 5, 175-82. DOI: 10.14235/bs.2017.811.

[17] Rishniw, M., Rodriguez, P., Que, J., Burke, Z. D., Tosh, D., Chen, H., & Chen, X. (2011). Molecular aspects of esophageal development. Annals of the New York Academy of Sciences, 1232(1), 309-315. doi: 10.1111/j.1749-6632.2011.06071.x.

[18] Sapin, M. R., Nikolenko, V. N., Chava, S. V., Alekseeva, T. N., & Nikityuk, D. B. (2013). Questions classification and morphogenesis of the glands of the walls of hollow internal organs. Journal of Anatomy and Histopathology, 1, 9-17.

[19] Sadler, T. V. (2001). Medical Embryology by Langman (textbook). Translation from English Edited by O.D. Lutsyk. Lviv: Nautilus. ISBN: 966-95745-3-6.

[20] Seery, J. P. (2002). Stem cells of the oesophageal epithelium. Journal of cell science, 115, 1783-1789.

[21] Ventura, A., do Nascimento, A. A., dos Santos, M. A. J., Vieira-Lopes, D. A., Sales, A., & Pinheiro, N. L. (2013). Histological Description of Morphogenesis of the Gastroesophageal Mucosa of Gallus gallus Domesticus (Linnaeus, 1758). International Journal of Morphology, 31(4), 1331-1339. DOI: 10.4067/S0717-95022013000400030

[22] Wang, D. H., Tiwari, A., Kim, M. E., Clemons, N. J., Regmi, N. L., Hodges, W. A., ... & Zhang, Q. (2014). Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett’s metaplasia. The Journal of clinical investigation, 124(9), 3767-3780. doi: 10.1172/JCI66603.

[23] Wang, X., Ouyang, H., Yamamoto, Y., Kumar, P. A., Wei, T. S., Dagher, R., ... & Crum, C. P. (2011). Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell, 145(7), 1023-1035. doi: 10.1016/j.

[24] Weaver, J. M., Ross-Innes, C. S., Shannon, N., Lynch, A. G., Forshew, T., Barbera, M. ... Fitzgerald, R. C. (2014). Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nature genetics, 46(8), 837-843. doi: 10.1038/ng.3013

[25] Willet, S. G., & Mills, J. C. (2016). Stomach organ and cell lineage differentiation: from embryogenesis to adult homeostasis. Cellular and molecular gastroenterology and hepatology, 2(5), 546-559. DOI: 10.1016/j.jcmgh.2016.05.006

[26] Zhang, Y., Jiang, M., Kim, E., Lin, S., Liu, K., Lan, X., & Que, J. (2017). Development and stem cells of the esophagus. In: Seminars in cell & developmental biology, 66, 25-35. Academic Press. doi: 10.1016/j.semcdb.2016.12.008

[27] Zhou, H., Greco, M. A., Daum, F., & Kahn, E. (2001). Origin of cardiac mucosa: ontogenic consideration. Pediatric and developmental pathology, 4(4), 358-363.
Published
2018-12-27
How to Cite
Rekun, T., Vernygorodskyi, S., Kyselova, T., Tataryna, O., & Cherepakha, O. (2018). The role of the transcription factor Sox2 and cytokeratins in the formation and development of the gastroesophageal junction epithelial cell differon. Reports of Morphology, 24(4), 58-65. https://doi.org/https://doi.org/10.31393/morphology-journal-2018-24(4)-09