We screened expressed sequence tag databases for genes with up-regulated expression in inflammatory bowel diseases. A gene encoding a regenerating protein (REG)-like protein called RELP was identified and characterized. The relp gene encodes a major transcript of 1518 nucleotides, and two truncated splice variants. Unlike the reg genes, which form a cluster in chromosome 2, relp maps to chromosome 1p12-13.1. The predicted translation product is a 158-amino acid preprotein, showing 43% to 47% similarity to the REG proteins. It contains a 22-amino acid signal peptide, and a conserved calcium-dependent carbohydrate-recognition domain. Complementary DNA for the orthologous mouse gene was also cloned. The RELP protein is constitutively expressed in epithelial neuroendocrine cells of the small intestine and in parietal cells of the gastric mucosa. An up-regulated expression of RELP was seen in epithelial cells of inflammatory mucosa in ulcerative colitis and Crohn's disease, in regenerating epithelial borders of gastric ulcers, and in metaplastic epithelium in the antrum and the esophagus. Our findings suggest that RELP might be involved in inflammatory and metaplastic responses of the gastrointestinal epithelium.

The regenerating protein (Reg)-like protein (RELP, also known as Reg IV) is a recently characterized fourth member of the human Reg protein family. The Reg proteins are small, about 20-kD-sized, secretory proteins of C-lectin type. The previously known Reg proteins have been functionally implicated in regeneration, proliferation, and differentiation of the pancreas, liver, and gastrointestinal mucosa. To study the tissue expression of RELP, we raised a monoclonal antibody to RELP. By immunohistochemistry and in situ hybridization, we found a robust de novo expression of RELP in the neoplastic goblet cells of appendiceal mucinous cystadenomas and in the epithelial implants of pseudomyxoma peritonei (PMP). Our findings indicate that RELP serves as a marker for appendiceal mucinous cystadenomas and PMP, and that RELP may contribute to the pathogenesis of these disorders.

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