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 factor (TFF)1 is synthesized and secreted by the normal stomach mucosa and by the gastrointestinal cells of injured tissues. The link between mouse TFF1 inactivation and the fully penetrant antropyloric tumor phenotype prompted the classification of TFF1 as a gastric tumor suppressor gene. Accordingly, altered expression, deletion, and/or mutations of the TFF1 gene are frequently observed in human gastric carcinomas. The present study was undertaken to address the nature of the cellular and molecular mechanisms targeted by TFF1 signalling. TFF1 effects were investigated in IEC18, HCT116, and AGS gastrointestinal cells treated with recombinant human TFF1, and in stably transfected HCT116 cells synthesizing constitutive or doxycycline-induced human TFF1. We observed that TFF1 triggers two types of cellular responses. On one hand, TFF1 lowers cell proliferation by delaying G1-S cell phase transition. This results from a TFF1-mediated increase in the levels of cyclin-dependent kinase inhibitors of both the INK4 and CIP subfamilies, leading to lower E2F transcriptional activity. On the other hand, TFF1 protects cells from chemical-, anchorage-free-, or Bad-induced apoptosis. In this process, TFF1 signalling targets the active form of caspase-9. Together, these results provide the first evidence of a dual antiproliferative and antiapoptotic role for TFF1. Similar paradoxical functions have been reported for tumor suppressor genes involved in cell differentiation, a function consistent with TFF1.
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PMID:The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis. 1203 70

Our previous studies have demonstrated that the total triterpenes from the fruits of Chaenomeles speciosa (CSTT) exhibit effective therapeutic effects on gastric ulcer patients and animals. The present aim is to further investigate the mechanisms involved. The results indicated that CSTT could ameliorate IND-induced gastric injury, which was related to promoting IND-damaged GES-1 cell proliferation and migration, improving the IND-damaged rat GBF, ulcer area, inhibition rate and pathologic changes of gastric mucous tissue, increasing the amount of adhered gastric mucus, attenuating the volume and total acidity of the gastric effluents, and augmenting the gastric pH; further studies showed that CSTT obviously downregulated miR-423-5p mRNA, NAG-1 mRNA and protein expression, Bax, Bad, cytosol cytochrome C, Apaf-1, cleaved-caspase-3, and cleaved-caspase-9 protein expression and cytosol cytochrome C concentration, and upregulated TFF1, TFF2 and TFF3 mRNA and protein expression, Bcl-2, Bcl-xl, pro-caspase-3, and pro-caspase-9 protein expression, mitochondrial viability, mitochondrial cytochrome C concentration and Bcl-2/Bax, Bcl-xl/Bad ratios. These findings demonstrated that CSTT protected against IND-induced gastric damage by depressing miR-423-5p expression and modulating the TFF/NAG-1 pathway, which in turn restrained mitochondrion-mediated apoptosis.
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PMID:Total triterpenoids from the fruits of Chaenomeles speciosa exerted gastroprotective activities on indomethacin-induced gastric damage via modulating microRNA-423-5p-mediated TFF/NAG-1 and apoptotic pathways. 3189 80