Crypt Proliferation and Growth Factor Expression in Acute Indomethacin-Induced Small Intestinal Injury
NSAIDs cause small intestinal mucosal injuries, but early events within the mucosa have not been clarified. The aim of this study was to characterize early changes in both crypt proliferation and the expression of growth factors in indomethacin-induced small intestinal damage. Crypt proliferation and intestinal mRNA expression of TGF-/β1, IGF-1, HGF, and NGF were investigated in rats that received 24 mg/kg of intracolonic indomethacin. Proliferation was assessed by immunohistochemical staining for 5'- bromo - 2'- deoxyuridine, and mRNA expression of growth factors was measured semi-quantitatively by reverse transcription (RT)-PCR. Crypt proliferation in the mid-small intestine did not decrease at two hours after administration of indomethacin but that in the jejunum and the ileum decreased significantly. Crypt proliferation was decreased at all sites after six hours. TGF-/βl, IGF -1 and HGF mRNA expression increased until six hours, whereas NGF showed no such increase. Early mucosal damage induced by indomethacin is characterized by alteration of the crypt architecture without changes in crypt cell proliferation. NGF may play a role in the progression of this mucosal damage.