Gastrin increases murine intestinal crypt regeneration following injury.
Abstract
A number of growth factors affect the regeneration of intestinal epithelia following injury, but the effects of amidated gastrin have not previously been assessed. We therefore investigated the effects of gastrin on intestinal regeneration following a range of stimuli. Intestinal crypt regeneration was assessed in transgenic mice overexpressing amidated gastrin (INS-GAS) and mice in which hypergastrinemia was induced using omeprazole, following gamma-radiation, 5-fluorouracil, and dextran sulphate sodium (DSS). Abundance of the CCK-2 receptor was assessed in intestinal epithelia and IEC-6 intestinal epithelial cells following gamma-radiation. Four days following 14 Gy gamma-radiation, or 2 injections of 400 mg/kg 5-fluorouracil, INS-GAS mice exhibited significantly increased small intestinal and colonic crypt survival compared with their wild-type counterparts (FVB/N). INS-GAS mice treated with 3% DSS for 5 days showed less weight loss and increased colonic crypt regeneration at 8 days compared with FVB/N. Increased small intestinal and colonic crypt survival was also demonstrated following gamma-radiation in FVB/N mice rendered hypergastrinemic using omeprazole. The increased crypt survival in INS-GAS mice following 14 Gy gamm...Continue Reading
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