ABSTRACT
Tff peptides are secreted mainly by the gastrointestinal epithelial cells and their primary role is maintaining normal structure and function of mucous epithelia. Ongoing studies on their expression pattern have disclosed other sites of their synthesis thus revealing additional physiological functions in the organism. Here we present new data about Tff3 expression in the cochlea of the rodent inner ear. On the basis of RT-PCR we describe the presence of Tff3 transcripts in both, a mouse cDNA library isolated from whole cochleae from postnatal days 3-15 (P3-P15), and also in cochlear tissue. By using a riboprobe for the fragment containing exon 1, 2 and 3 of Tff3, in situ hybridization, localized Tff3 signals in neurons of spiral ganglion and vestibular organ. We did not observe any abnormalities in the middle ear of Tff3 knock-out mice, neither did histological examination of the inner ear indicate any gross morphological changes in the cochlea. However, ABR (auditory evoked brain stem responses) audiograms revealed that the Tff3 knock-out animals show an accelerated presbyacusis and a hearing loss of about 15 dB at low frequencies increasing to 25 dB loss at higher frequencies. These findings suggest that Tff3 could play a role in neurosensory signaling. Further studies are needed to clarify this new function in the auditory system.
Subject(s)
Hearing Loss/metabolism , Hearing Loss/physiopathology , Mucins/deficiency , Mucins/metabolism , Presbycusis/metabolism , Presbycusis/physiopathology , Animals , Disease Progression , Ear, Inner/cytology , Ear, Inner/metabolism , Ear, Middle/cytology , Ear, Middle/metabolism , Gene Expression Regulation , Hearing Loss/genetics , Hearing Loss/pathology , Mice , Mice, Knockout , Mucins/genetics , Presbycusis/genetics , Presbycusis/pathology , RNA, Messenger/genetics , Trefoil Factor-3ABSTRACT
Trefoil factor family (TFF) peptides are major secretory products of mucous epithelia and play a multifunctional role in cytoprotection, apoptosis, and immune response. Recently, a TFF2-binding protein was discovered in mice and named blottin. It is down-regulated in gastric cancer (GDDR), abundant in human gastric surface (TFIZ1) and its similarity to gastrokine-1 led to the gene's name GKN2. To investigate the mode of GKN2 regulation activity of a luciferase reporter gene, controlled by the GKN2 promoter, was monitored upon treatment with various pro-inflammatory (TNF-alpha, IL-1beta, IL-6, IFN-gamma) and anti-inflammatory (TGF-beta1) cytokines using gastric (AGS, KATO III) and colonic (HT-29) cell lines. To assess the direct role of transcription factors (NFkappaB, HNF-3beta, hGATA6) in regulating GKN2 we performed transient co-transfection of their expression plasmids and the reporter gene construct. GKN2 gene was down-regulated by pro-inflammatory cytokines in all tested cell lines while up-regulated by TGF-beta1 only in the colonic cell line. GKN2 expression was significantly reduced in both gastric adenocarcinoma cell lines by the active form of NFkappaB transcription factor, whereas in the colonic cell line an up-regulation was noticed. Down-regulation by IL-6 was mediated by C/EBPbeta transcription factor in case of HT-29 but not of KATO III cells. We conclude that the regulation of GKN2 parallels that of TFF genes, indicating that together they may play an important role in maintaining the homeostasis of the gastrointestinal tract.
Subject(s)
Carrier Proteins/metabolism , Cytokines/pharmacology , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Base Sequence , Binding Sites , CCAAT-Enhancer-Binding Protein-beta/genetics , CCAAT-Enhancer-Binding Protein-beta/metabolism , Carrier Proteins/genetics , Cell Line , DNA Primers/genetics , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Gastrointestinal Tract/cytology , Gene Expression Regulation/drug effects , Humans , Interleukin-6/pharmacology , NF-kappa B/genetics , NF-kappa B/metabolism , Promoter Regions, Genetic , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacology , Transcription Factors/genetics , Transcription Factors/metabolism , Transfection , Trefoil Factor-2ABSTRACT
In this study we present a 102-year old woman carrying a (7;12)(q11.3;q14) translocation. A woman displays a normal phenotype and infertility in anamnesis. This is the first report linking t(7;12) and infertility.
