Alterations in gene expression and microbiome composition upon calcium sensing receptor deletion in the mouse esophagus

We reported previously that CaSR can be conditionally deleted in the mouse esophagus. This conditional knock-out (KO) model showed significant reduction in levels of adherens and tight junction proteins and had marked build-up of bacteria on the luminal esophageal surface. To further examine the role of CaSR, we used RNA sequencing to determine gene expression profiles in esophageal epithelia of control and conditional KO mice (EsoCaSR-/-). RNA Seq data indicated upregulation of gene sets involved in DNA replication and cell cycle in EsoCaSR-/-. This is accompanied by downregulation of gene sets involved in the innate immune response and in protein homeostasis including peptide elongation and protein trafficking. Ingenuity Pathway Analysis (IPA) demonstrated that these genes are mapped to important biological networks including Calcium and RhoA signaling pathways. To further explore the bacterial buildup in EsoCaSR-/- esophageal tissue, 16S sequencing of the mucosal-associated bacterial microbiome was performed. Three bacterial species, g_Rodentibacter, s_Rodentibacter_unclassified, and s_Lactobacillus_hilgardi were significantly increased in EsoCaSR-/-. Furthermore, metagenomic analysis of 16S sequences indicated that pathways related to oxidative phosphorylation and metabolism were downregulated in EsoCaSR-/- tissues. These data demonstrate that CaSR impacts major pathways of cell proliferation, differentiation, cell cycle and innate immune response in esophageal epithelium...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research