| dc.description.abstract | Gastric cancer presents a significant global health challenge. This thesis explores the interplay of intrinsic and extrinsic factors driving gastric metaplasia, a precursor to gastric cancer. It particularly focuses on the role of miR-148a in chief cells and the involvement of telocytes in the gastric microenvironment. Chief cell transdifferentiation and the response of the microenvironment to injury are pivotal in metaplasia development, influencing the progression toward gastric carcinogenesis. A significant discovery of this research is the identification of miR-148a as a key intrinsic factor. Highly expressed in chief cells, miR-148a undergoes significant downregulation during the transdifferentiation of chief cells into spasmolytic polypeptide-expressing metaplasia (SPEM) cells. This downregulation coincides with the onset of metaplastic changes, suggesting a crucial role for miR-148a in initiating chief cell transdifferentiation in response to gastric tissue injury and contributing to the development of metaplasia. Parallel to the examination of intrinsic cellular changes, the thesis introduces telocytes as novel extrinsic factors in the gastric microenvironment. Characterized by their expression of FOXL1 and PDGFRα, telocytes are shown to undergo notable changes in abundance and distribution in response to metaplasia development. Their strategic positioning and dynamic redistribution suggest their recruitment in shaping the metaplastic niche, particularly through WNT signaling pathways. This research provides a comprehensive understanding of the factors involved in metaplasia development in the stomach, highlighting the interplay between chief cell intrinsic mechanisms and extrinsic stromal influences. The insights gained are instrumental for advancing our understanding of gastric carcinogenesis. | |
