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)

The six-cysteine P-domain motif forms the basic repeat unit of a growing family of mucin-associated peptides. A precursor for a human secretory polypeptide has been discovered by molecular cloning and deduced to have a single P-domain, termed hP1.B. The pre-pro-peptide has 67% amino acid identity with rat intestinal trefoil factor. We find, using the techniques of RNA analysis and in situ hybridization, that this P-domain peptide is expressed in the human gastrointestinal tract, where a number of pathological conditions affect its expression, and surprisingly 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 synthesized and secreted additionally by the ulcer-associated cell lineage that is known to secrete two other trefoil peptides, pS2 and spasmolytic polypeptide (hSP). In the stomach, hP1.B mRNA is relatively scarce but is more abundant in foci of intestinal metaplasia and near to ulceration. Mucin-rich epithelial cells in hyperplastic polyps of the colon 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 maintenance and repair of mucosal function.
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PMID: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. 834 3

Mucin core proteins are expressed in a tissue and cell type specific manner in the normal gastrointestinal tract. Aberrant expression of mucin core proteins have been reported in colorectal neoplasms. To examine the relationship between subsets of colorectal polyps and non-mucinous and mucinous adenocarcinomas of the colorectum, we evaluated the frequency of the expression of cell lineage associated mucin core proteins (MUC5AC and MUC2), trefoil factors (TFF1 and TFF3), and APC and p21 in these tissues. An immunohistochemical study was performed in 10 normal rectal mucosa samples (NM) 21 hyperplastic polyps (HP), 20 serrated adenomas (SA), 25 tubular adenomas (TA), 13 tubulovillous adenomas (TVA), 7 villous adenomas (VA), 42 non-mucinous colorectal cancers (NMC), and 19 mucinous colorectal cancers (MC). A higher frequency of ectopic expression of gastric foveolar mucin, MUC5AC, and the expression of intestinal goblet cell mucins, MUC2, was observed respectively in HP (100%, 100%), SA (85%, 85%), TVA (85%, 85%), and VA (100%, 100%), compared to TA (32%, p<0.002; 36%, p<0.01). MC (68%, 100%) also showed a higher frequency of the expression of MUC5AC and MUC2 compared to NMC (31%, p=0.001; 38%, p<0.001), and TFF1 showed similar patterns of expression. APC protein and p21 were also expressed at a higher frequency in HP (100%, 100%), and SA (67%, 83%), than in TA (29%, p<0.03; 46%, p<0.05). MC (68%, 100%) showed a higher frequency of expression of APC protein and p21 than NMC (19%, p<0.001; 45%, p<0.01). Our results showed that MUC2 expression and de novo ectopic expression of MUC5AC and TFF1 are more frequent in HP, SA, TVA, VA, and MC than in TA and NMC. These results suggest that simultaneous activation of differentiation pathways of goblet cells and gastric foveolar cells may occur predominantly in the pathogenesis of HP, SA, TVA, VA, and MC, while the pathogenesis of TA and NMC are less likely to involve these processes.
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PMID:Expression of mucin core proteins, trefoil factors, APC and p21 in subsets of colorectal polyps and cancers suggests a distinct pathway of pathogenesis of mucinous carcinoma of the colorectum. 1614 11

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease.
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PMID:Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis. 1692 27