The mechanism of intestinal stem cells differentiation after ischemia–reperfusion injury in a rat model

Purpose: Notch and Wnt/β-catenin signaling are responsible for regulation of intestinal stem cells (ISCs) proliferation and differentiation. The purpose of the study was to evaluate Wnt/β-catenin and Notch signaling roles in regulation of ISC differentiation following ischemia–reperfusion (IR) injury in a rat. Methods: Rats were assigned into two groups: Sham rats underwent laparotomy without vascular intervention and IR rats underwent occlusion of SMA and portal vein for 20 min followed by 48 h of reperfusion. Wnt/β-catenin and Notch-related gene expression were determined using Real-Time PCR. Enterocyte proliferation, differentiation and Wnt-related proteins were determined by immunohistochemistry. Results: IR rats demonstrated a significant decrease in β-catenin gene expression, a decrease in cyclin D1 and β-catenin positive cells in jejunum and ileum compared to Sham rats. IR rats demonstrated a significant increase in Notch-related gene expression in jejunum and ileum compared to Sham rats. The number of secretory cells was higher mainly in the jejunum and number of absorptive cells was significantly lower in jejunum and lower in ileum in IR rats compared to Sham rats. Conclusions: Intestinal stem-cell differentiation is toward secretory cells 48 h after IR injury; however, Wnt/β-catenin pathway inhibition and Notch-related gene expression stimulation suggest crosstalk between pathways.