HP1.B, A HUMAN P-DOMAIN PEPTIDE HOMOLOGOUS WITH RAT INTESTINAL TREFOIL FACTOR, IS EXPRESSED ALSO IN THE ULCER-ASSOCIATED CELL LINEAGE AND THE UTERUS

The six-cysteine P-domain motif forms the basic repeat unit of a growi ng family of mucin-associated peptides. A precursor for a human secret ory polypeptide has been discovered by molecular cloning and deduced t o have a single P-domain, termed hP1.B. The pre-pro-peptide has 67% am ino acid identity with rat intestinal trefoil factor. We find, using t he techniques of RNA analysis and in situ hybridization, that this P-d omain peptide is expressed in the human gastrointestinal tract, where a number of pathological conditions affect its expression, and surpris ingly find it is expressed in the uterus also. In the intestine, hP1.B is expressed by goblet cells, but in Crohn disease this peptide is sy nthesized and secreted additionally by the ulcer-associated cell linea ge that is known to secrete two other trefoil peptides, pS2 and spasmo lytic polypeptide (hSP). In the stomach, hP1.B mRNA is relatively scar ce but is more abundant in foci of intestinal metaplasia and near to u lceration. Mucin-rich epithelial cells in hyperplastic polyps of the c olon also express this peptide. The discovery-of this P-domain peptide and its expression in association with mucins support the hypothesis that P-domains with mucins may subserve related functions in the maint enance and repair of mucosal function.