Effect of CaSR Deletion in the Esophagus on Gene Expression and Immune Function

Background: The calcium sensing receptor (CaSR) regulates Ca2+ concentration in plasma by regulating parathyroid hormone secretion. In other tissues, CaSR plays roles in cellular differentiation and migration, and in secretion and absorption. We reported previously that CaSR can be conditionally deleted in the mouse esophagus. This conditional knock-out ( EsoCaSR−/−) model showed significant reduction in levels of adherens and tight junction proteins and had significant build-up of bacteria on the luminal esophageal surface. Objectives: We aimed to further understand the role of CaSR and to examine the modification in gene expression induced by CaSR deletion in the esophagus. Methods: We performed mRNA sequencing and bioinformatic analyses of mice esophageal tissues. Gene expression was characterized using an unbiased pathway approach in EsoCaSR−/− and control mouse esophageal mucosae. Next generation sequencing was used to obtain a profile of the differences in RNA expression between tissues. RNA expression data was used to analyze differences in pathways and functional networks between EsoCaSR−/− and control esophageal tissues. Results: Our data indicated significant upregulation of gene sets involved in DNA replication and cell cycle in EsoCaSR−/−. This is accompanied by marked downregulation of gene sets involved in the innate immune response and in protein homeostasis including peptide elongation and protein traffcking. Ingenuity Pathway Analysis (IPA) demonstrated that these genes are mapped to important biological networks including Calcium and RhoA signaling pathways. Conclusions: The major findings of this study are that CaSR impacts important pathways of cell proliferation, differentiation, cell cycle and innate immune response in esophageal epithelium. The disruption of these pathways also causes significant modifications of the microbiome. Funding: U54 GM104940 grant from NIH, VA Merit grant, Paul Teschan Research grant, Carol Lavin Bernick grant, Tulane institutional grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.