Arsenic exposure affects Pdgfrα stromal cells in the ileum of the small intestine

Abstract

Arsenic is a contaminant in drinking water and food, and exposure induces inflammation and barrier disruption in the small intestine and colon. Further, arsenic can alter stromal cell numbers and their signaling molecules in the duodenum. Thus, the goal of this study was to investigate arsenic's effects on morphology, Pdgfrα⁺ stromal cell numbers, localization, and signaling in the ileum. Mice were exposed to 0, 100, and 500 ppb arsenic for 13 weeks, and intestinal sections, including the ileum, dissected out. The results show that arsenic dose-responsive increases in crypt budding and macrophage numbers in the ileum. Arsenic exposure also increased transcript expression of telocyte (Cd201, Tmem158, Wnt4), trophocyte (Ackr4, Grem1), Igfbp5+ fibroblast (Igfbp5), and Fgfr2+ fibroblast (Fgfr2, Igfbp3, Wnt4) markers in the ileum of female mice, but not in the males. Linear regression indicated that markers of telocytes and Fgfr2+ fibroblasts significantly correlated with Wnt4 expression. IHC revealed the numbers of telocytes within the villi of male and females were increased by 6.3- and 2.3-fold at 500 ppb, respectively. Linear regression of Grem1 versus Bmp4 protein expression revealed significant correlation, with arsenic exposed females having higher expression of both signaling molecules. Overall, the results suggest that Pdgfrα+ stromal cells in the ileum play vital roles in maintaining intestinal stem cell (ISC) and epithelial homeostasis in response to arsenic, and that sex-dependent changes in responses exist.