Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trefoil peptides are a growing group of proteins with interesting structural and functional properties. We have defined the pattern of trefoil peptide gene expression in the ulceration-associated cell lineage (UACL) and in the nearby mucosa in Crohn's disease. In the UACL, human spasmolytic polypeptide (hSP) mRNA is expressed in the acinar and proximal duct cells, while pS2 mRNA and peptide are found in the distal duct cells and in the surface cells. In adjacent mucosa, pS2 mRNA and protein are expressed by goblet cells, with the pS2 peptide concentrated in the area of the Golgi and also in the theca. Ultrastructural immunolocalisation showed the pS2 to be co-packaged in the mucous cell granules before being secreted into the intestinal lumen. In addition, pS2 peptide was demonstrated in local neuroendocrine cells and was also co-packaged with the neuroendocrine granules. The crypts associated with the UACL also showed marked neuroendocrine cell hyperplasia. We conclude that pS2 peptide is secreted locally into the viscoelastic coat covering the intestinal mucosa which surrounds Crohn's disease ulcers. In addition, it is clear that intestinal goblet cells, in addition to producing mucins, are a rich source of regulatory peptides. Moreover, pS2 is clearly co-packaged with neurosecretory granules, which are released through basal and lateral membranes so that the contained peptides can act in a paracrine manner. These findings are interpreted in terms of the epidermal growth factor/urogastrone released by the UACL, stimulating pS2 gene expression in surrounding cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease. 129 63

Hyperplastic polyps are common benign lesions of uncertain histogenesis, which occur in the colon in populations at risk for colorectal carcinoma. They contain neutral/MUC1 gene-related mucin which in turn is closely associated with the trefoil-peptide pS2, a major component of the ulcer-associated cell lineage, previously termed pseudopyloric metaplasia. We have examined 17 hyperplastic polyps for expression of the trefoil-peptides pS2 and human spasmolytic polypeptide by in situ hybridization and immunohistochemistry, as well as by using antisera to epidermal growth factor/urogastrone and its receptor and to epitopes of the product of the MUC1 gene to characterize any further similarity between these lesions and the ulcer-associated cell lineage and thus help elucidate the nature of the lesions. Our investigations show both human spasmolytic polypeptide and pS2 messenger RNA within the polyps, whereas only pS2 peptide could be demonstrated immunohistochemically. Epidermal growth factor/urogastrone, its receptor, and antisera to the MUC1 gene also showed widespread staining of these polyps. We suggest that hyperplastic polyps are formed of a lineage that both synthesizes and secretes trefoil-peptides and the MUC1 mucin and that hyperplastic polyps may be related to the phenotypically similar ulceration-associated cell lineage.
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PMID:Hyperplastic polyps: a cell lineage which both synthesizes and secretes trefoil-peptides and has phenotypic similarity with the ulcer-associated cell lineage. 768 Dec 55

The ulceration-associated cell lineage (UACL) develops in the human gastrointestinal mucosa after ulceration; it grows out from the bases of adjacent crypts and ramifies in the lamina propria to form a new gland, finally giving rise to a duct by which the glandular secretion and indeed cells are carried to the surface. Using immunocytochemistry and in situ hybridization with 35S-labelled riboprobes, we have defined the pattern of trefoil peptide gene expression (pS2; human spasmolytic polypeptide, hSP), epidermal growth factor/urogastrone (EGF/URO), and the distribution of cell proliferation during the development of the UACL, as indicated by immunostaining for proliferating cell nuclear antigen (PCNA). Our studies reveal that the morphogenesis of the UACL shows a marked morphological resemblance to developing Brunner's glands; the pattern of trefoil peptide gene expression during UACL development is also very similar. However, trefoil peptide gene expression in the mature UACL complex is unique amongst gastrointestinal cells. The mature UACL shows a distinctive proliferative organization: while the early buds and glands are non-proliferative, apparently being fed by cells from the parent crypts, a definitive proliferative zone develops within the duct. This, of course, corresponds to the location of the gastric gland proliferative zone. We propose that while the UACL shows novel features, it shares its differentiation programme with Brunner's glands, but its pattern of cell renewal eventually is that of the gastric gland.
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PMID:The ulceration-associated cell lineage (UACL) reiterates the Brunner's gland differentiation programme but acquires the proliferative organization of the gastric gland. 796 91

Members of the trefoil family of peptides are generally small stable secreted molecules, structurally related by the presence of one, or up to six, compact 6-cysteine motifs. Several trefoil peptides are expressed in mammalian gut and Xenopus gut and skin, often in association with mucins. Chronic ulcerative conditions of the gut, such as Crohn's disease, result in the growth of glandular structures of the ulcer-associated cell lineage (UACL) that secrete epidermal growth factor/urogastrone, transforming growth factor-alpha, and at least three trefoil peptides [pS2, human spasmolytic polypeptide (hSP), and intestinal trefoil factor (hITF/hP1.B)]. Neuroendocrine and goblet cells near the UACL are "recruited" into expressing pS2 and hSP, but the purpose of this concerted expression is unclear. A role in mucosal healing has been proposed. Biological functions of trefoil peptides have been difficult to establish. Pancreatic spasmolytic polypeptide of porcine origin inhibits gastric acid secretion and smooth muscle contraction and is a growth factor for some cultured cells, but pS2, once thought to be breast cancer specific, is not a mitogen. Recombinant trefoil peptides have allowed localization of binding sites and will allow structure-activity relationships to be studied, once the functions are clear.
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PMID:Trefoil peptides: a newly recognized family of epithelial mucin-associated molecules. 836 6