Expression of Reg family genes in the gastrointestinal tract of mice treated with indomethacin.

Regenerating gene (Reg) family proteins, which are classified into four types, commonly act as trophic and/or antiapoptotic factors in gastrointestinal (GI) diseases. However, it remains unclear how these proteins coordinate their similar roles under such pathophysiological conditions. Here, we investigated the interrelationships of Reg family gene expression with mucosal cell proliferation and apoptosis in nonsteroidal anti-inflammatory drug (NSAID)-induced GI injury. GI injury was induced by subcutaneous injection of indomethacin into Reg I knockout (KO) and wild-type (WT) mice, and its severity was scored histopathologically. Temporal changes in the expression of Reg family genes, mucosal proliferation, and apoptosis were evaluated throughout the GI tract by real-time RT-PCR, Ki-67 immunoreactivity, and TUNEL assay, respectively. Reg I, Reg III family, and Reg IV were predominantly expressed in the upper, middle, and lower GI mucosa, respectively. Expression of Reg I and Reg III family genes was upregulated in specific portions of the GI tract after indomethacin treatment. Ki-67-positive epithelial cells were significantly decreased in the gastric and small-intestinal mucosa of Reg I KO mice under normal conditions. After treatment with indomethacin, the number of TUNEL-positive cells was significantly greater throughout the GI mucosa in Reg I KO mice than in WT mice. Expression of Reg I was independent of that of other Reg family genes in, not only normal GI tissues, but also indomethacin-induced GI lesions. Members of the Reg gene family show distinct profiles of expression in the GI tract, and Reg I independently plays a role in protecting the GI mucosa against NSAID-induced injury.