Trefoil factor 3: Difference between revisions

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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Trefoil factor 3''' is a [[protein]] that in humans is encoded by the ''TFF3'' [[gene]].<ref name="pmid7718582">{{cite journal |vauthors=Thim L, Woldike HF, Nielsen PF, Christensen M, Lynch-Devaney K, Podolsky DK | title = Characterization of human and rat intestinal trefoil factor produced in yeast | journal = Biochemistry | volume = 34 | issue = 14 | pages = 4757–64 |date=May 1995 | pmid = 7718582 | pmc =  | doi =10.1021/bi00014a033  }}</ref><ref name="pmid9043862">{{cite journal |vauthors=Gott P, Beck S, Machado JC, Carneiro F, Schmitt H, Blin N | title = Human trefoil peptides: genomic structure in 21q22.3 and coordinated expression | journal = Eur J Hum Genet | volume = 4 | issue = 6 | pages = 308–15 |date=May 1997 | pmid = 9043862 | pmc = | doi = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TFF3 trefoil factor 3 (intestinal)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7033| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_TFF3_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1e9t.
| PDB = {{PDB2|1e9t}}, {{PDB2|1pe3}}
| Name = Trefoil factor 3 (intestinal)
| HGNCid = 11757
| Symbol = TFF3
| AltSymbols =; HITF; ITF; TFI; hP1.B
| OMIM = 600633
| ECnumber = 
| Homologene = 2427
| MGIid = 104638
| GeneAtlas_image1 = PBB_GE_TFF3_204623_at_tn.png
| Function =  
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0030141 |text = secretory granule}}
| Process = {{GNF_GO|id=GO:0006952 |text = defense response}} {{GNF_GO|id=GO:0007586 |text = digestion}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7033
    | Hs_Ensembl = ENSG00000160180
    | Hs_RefseqProtein = NP_003217
    | Hs_RefseqmRNA = NM_003226
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 21
    | Hs_GenLoc_start = 42599751
    | Hs_GenLoc_end = 42608775
    | Hs_Uniprot = Q07654
    | Mm_EntrezGene = 21786
    | Mm_Ensembl = ENSMUSG00000024029
    | Mm_RefseqmRNA = NM_011575
    | Mm_RefseqProtein = NP_035705
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 17
    | Mm_GenLoc_start = 30852327
    | Mm_GenLoc_end = 30856623
    | Mm_Uniprot = Q62395
  }}
}}
'''Trefoil factor 3 (intestinal)''', also known as '''TFF3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TFF3 trefoil factor 3 (intestinal)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7033| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Members of the trefoil family are characterized by having at least one copy of the [[trefoil domain|trefoil motif]], a 40-amino acid domain that contains three conserved [[disulfide bond]]s. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. This gene is a marker of columnar epithelium and is expressed in a variety of tissues including goblet cells of the intestines and colon. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.<ref name="entrez" />
{{PBB_Summary
 
| section_title =
=== In breast milk ===
| summary_text = Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. This gene is expressed in goblet cells of the intestines and colon. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.<ref name="entrez">{{cite web | title = Entrez Gene: TFF3 trefoil factor 3 (intestinal)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7033| accessdate = }}</ref>
 
}}
Trefoil factors (TFF) are secretory products of mucin producing cells. They play a key role in the maintenance of the surface integrity of oral mucosa and enhance healing of the gastrointestinal mucosa by a process called restitution. TFF comprises the gastric peptides ([[TFF1]]), spasmolytic peptide ([[TFF2]]), and the intestinal trefoil factor (TFF3, this protein). They have an important and necessary role in epithelial restitution within the gastrointestinal tract. Significant amounts of TFF are present in human milk. Evidence has been presented that TFF3 isolated from milk strongly correlates with downregulation of [[interleukin 6|IL-6]] and [[interleukin 8|IL-8]] in human intestinal epithelial cells. On the other hand, TFF3 activated the epithelial cells in culture to produce beta defensins 2 (hBD2) and beta defensins 4 (hBD4). These findings suggest that TFF can activate intestinal epithelial cells and could actively participate in the immune system of breastfed babies by inducing the production of peptides related to innate defence, such as defensins.<ref name="pmid23198942">{{cite journal |vauthors=Barrera GJ, Sanchez G, Gonzalez JE | title = Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29 | journal = Bosn J Basic Med Sci | volume = 12 | issue = 4 | pages = 256–64 |date=November 2012 | pmid = 23198942 | pmc=4362502}}</ref>
 
=== Activation of PAR-2 receptors ===
 
Two main mechanisms have been described for the activation of PAR-2: (A) by specifi c cleavage that unmask the receptor-activating peptide sequence present in the extracellular N-terminal domain of each PAR, leading to cell signaling via interaction of the exposed tethered ligand with the body of the receptor itself; and (B) by synthetic peptides, such as SLIGKV, that bind to the receptor, mimicking the actions of agonist proteases.<ref name="Barrera_2016"/> During lactation, TFF3 secreted in human milk may activate intestinal epithelial cells through PAR-2 receptors, which in turn induces hBD2 and hBD4 expression and cytokine regulation.<ref name="Barrera_2016">{{cite journal | vauthors = Barrera GJ, Tortolero GS | title = Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins | journal = Bratislavské LekáRske Listy | volume = 117 | issue = 6 | pages = 332–9 | year = 2016 | pmid = 27546365 | doi = 10.4149/bll_2016_066}}</ref>
 
== Clinical significance ==
 
Using TFF3 as a marker of columnar epithelium, a process using an ingestible oesophageal sampling device (Cytosponge) coupled with immunocytochemistry for trefoil factor 3 to improve the accuracy and acceptability of the detection/screening of Barrett's oesophagus has been developed.<ref name="pmid20833740">{{cite journal |vauthors=Kadri SR, Lao-Sirieix P, O'Donovan M, Debiram I, Das M, Blazeby JM, Emery J, Boussioutas A, Morris H, Walter FM, Pharoah P, Hardwick RH, Fitzgerald RC | title = Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study | journal = BMJ | volume = 341 | issue = | pages = c4372 | year = 2010 | pmid = 20833740 | pmc = 2938899 | doi = 10.1136/bmj.c4372| url = }}</ref>
However the clinical utility of such a test may be limited by frequent staining of TFF3 in gastric cardia and subsequent risk of false positives.<ref name="pmid15177871">{{cite journal |vauthors=Peitz U, Kouznetsova I, Wex T, Gebert I, Vieth M, Roessner A, Hoffmann W, Malfertheiner P | title = TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD) | journal = Peptides | volume = 25 | issue = 5 | pages = 771–7 | year = 2004 | pmid = 15177871 | pmc = | doi = 10.1016/j.peptides.2004.01.018 | url =  }}</ref>


==References==
==References==
{{reflist|2}}
{{reflist}}
{{Clear}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  |vauthors=Barrera GJ, Sanchez G, Gonzalez JE |title=Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29 |journal=Bosn J Basic Med Sci. |volume=12 |issue= 4 |pages= 256–64 |year= 2012 |pmid= 23198942 |doi= |pmc=4362502}}
| citations =
*{{cite journal  |vauthors=Hoffmann W, Jagla W, Wiede A |title=Molecular medicine of TFF-peptides: from gut to brain |journal=Histol. Histopathol. |volume=16 |issue= 1 |pages= 319–34 |year= 2001 |pmid= 11193208 |doi=  }}
*{{cite journal  | author=Hoffmann W, Jagla W, Wiede A |title=Molecular medicine of TFF-peptides: from gut to brain. |journal=Histol. Histopathol. |volume=16 |issue= 1 |pages= 319-34 |year= 2001 |pmid= 11193208 |doi= }}
*{{cite journal  |vauthors=Hoffmann W, Jagla W |title=Cell type specific expression of secretory TFF peptides: colocalization with mucins and synthesis in the brain |journal=Int. Rev. Cytol. |volume=213 |issue= |pages= 147–81 |year= 2002 |pmid= 11837892 |doi=10.1016/S0074-7696(02)13014-2 | series=International Review of Cytology  | isbn=978-0-12-364617-0  }}
*{{cite journal  | author=Hoffmann W, Jagla W |title=Cell type specific expression of secretory TFF peptides: colocalization with mucins and synthesis in the brain. |journal=Int. Rev. Cytol. |volume=213 |issue= |pages= 147-81 |year= 2002 |pmid= 11837892 |doi=  }}
*{{cite journal  | author=Langer G |title=Ocular TFF-peptides: new mucus-associated secretory products of conjunctival goblet cells |journal=Adv. Exp. Med. Biol. |volume=506 |issue= Pt A |pages= 313–6 |year= 2003 |pmid= 12613926 |doi=  |name-list-format=vanc| author2=Jagla W  | author3=Behrens-Baumann W  | display-authors=3  | last4=Walter  | first4=S  | last5=Hoffmann  | first5=W  }}
*{{cite journal  | author=Langer G, Jagla W, Behrens-Baumann W, ''et al.'' |title=Ocular TFF-peptides: new mucus-associated secretory products of conjunctival goblet cells. |journal=Adv. Exp. Med. Biol. |volume=506 |issue= Pt A |pages= 313-6 |year= 2003 |pmid= 12613926 |doi=  }}
*{{cite journal  |vauthors=Seib T, Dooley S, Welter C |title=Characterization of the genomic structure and the promoter region of the human intestinal trefoil factor |journal=Biochem. Biophys. Res. Commun. |volume=214 |issue= 1 |pages= 195–9 |year= 1995 |pmid= 7669039 |doi= 10.1006/bbrc.1995.2274 }}
*{{cite journal  | author=Seib T, Dooley S, Welter C |title=Characterization of the genomic structure and the promoter region of the human intestinal trefoil factor. |journal=Biochem. Biophys. Res. Commun. |volume=214 |issue= 1 |pages= 195-9 |year= 1995 |pmid= 7669039 |doi= 10.1006/bbrc.1995.2274 }}
*{{cite journal  |vauthors=Podolsky DK, Gerken G, Eyking A, Cario E |title=Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency |journal=Gastroenterology |volume=137 |issue=1 |pages=209–20 |year=2009 |pmid= 19303021 |doi=10.1053/j.gastro.2009.03.007 |pmc=2812790}}
*{{cite journal | author=Thim L, Wöldike HF, Nielsen PF, ''et al.'' |title=Characterization of human and rat intestinal trefoil factor produced in yeast. |journal=Biochemistry |volume=34 |issue= 14 |pages= 4757-64 |year= 1995 |pmid= 7718582 |doi=  }}
*{{cite journal  | author=Hauser F |title=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 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 15 |pages= 6961–5 |year= 1993 |pmid= 8346203 |doi=10.1073/pnas.90.15.6961 | pmc=47055 |name-list-format=vanc| author2=Poulsom R | author3=Chinery R | display-authors=3  | last4=Rogers  | first4=LA  | last5=Hanby  | first5=AM  | last6=Wright  | first6=NA  | last7=Hoffmann  | first7=W  }}
*{{cite journal  | author=Hauser F, Poulsom R, Chinery R, ''et al.'' |title=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. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 15 |pages= 6961-5 |year= 1993 |pmid= 8346203 |doi= }}
*{{cite journal  | author=Podolsky DK |title=Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion |journal=J. Biol. Chem. |volume=268 |issue= 9 |pages= 6694–702 |year= 1993 |pmid= 8454642 |doi=  |name-list-format=vanc| author2=Lynch-Devaney K  | author3=Stow JL  | display-authors=3  | last4=Oates  | first4=P  | last5=Murgue  | first5=B  | last6=Debeaumont  | first6=M  | last7=Sands  | first7=BE  | last8=Mahida  | first8=YR }}
*{{cite journal  | author=Podolsky DK, Lynch-Devaney K, Stow JL, ''et al.'' |title=Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion. |journal=J. Biol. Chem. |volume=268 |issue= 9 |pages= 6694-702 |year= 1993 |pmid= 8454642 |doi= }}
*{{cite journal  | author=Schmitt H |title=A third P-domain peptide gene (TFF3), human intestinal trefoil factor, maps to 21q22.3 |journal=Cytogenet. Cell Genet. |volume=72 |issue= 4 |pages= 299–302 |year= 1996 |pmid= 8641134 |doi=10.1159/000134208 |name-list-format=vanc| author2=Wundrack I  | author3=Beck S  | display-authors=3  | last4=g&Ouml;Tt  | first4=P. | last5=Welter  | first5=C. | last6=Shizuya  | first6=H. | last7=Simon  | first7=M.I.  | last8=Biin  | first8=N. }}
*{{cite journal  | author=Schmitt H, Wundrack I, Beck S, ''et al.'' |title=A third P-domain peptide gene (TFF3), human intestinal trefoil factor, maps to 21q22.3. |journal=Cytogenet. Cell Genet. |volume=72 |issue= 4 |pages= 299-302 |year= 1996 |pmid= 8641134 |doi=  }}
*{{cite journal  |vauthors=Chinery R, Williamson J, Poulsom R |title=The gene encoding human intestinal trefoil factor (TFF3) is located on chromosome 21q22.3 clustered with other members of the trefoil peptide family |journal=Genomics |volume=32 |issue= 2 |pages= 281–4 |year= 1997 |pmid= 8833157 |doi= 10.1006/geno.1996.0117 }}
*{{cite journal | author=Chinery R, Williamson J, Poulsom R |title=The gene encoding human intestinal trefoil factor (TFF3) is located on chromosome 21q22.3 clustered with other members of the trefoil peptide family. |journal=Genomics |volume=32 |issue= 2 |pages= 281-4 |year= 1997 |pmid= 8833157 |doi= 10.1006/geno.1996.0117 }}
*{{cite journal  | author=Probst JC |title=Human intestinal trefoil factor is expressed in human hypothalamus and pituitary: evidence for a novel neuropeptide |journal=FASEB J. |volume=10 |issue= 13 |pages= 1518–23 |year= 1997 |pmid= 8940297 |doi=  |name-list-format=vanc| author2=Zetzsche T  | author3=Weber M | display-authors=3  | last4=Theilemann  | first4=P  | last5=Skutella  | first5=T  | last6=Landgraf  | first6=R  | last7=Jirikowski  | first7=GF }}
*{{cite journal  | author=Probst JC, Zetzsche T, Weber M, ''et al.'' |title=Human intestinal trefoil factor is expressed in human hypothalamus and pituitary: evidence for a novel neuropeptide. |journal=FASEB J. |volume=10 |issue= 13 |pages= 1518-23 |year= 1997 |pmid= 8940297 |doi=  }}
*{{cite journal  | author=Seib T |title=The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3 |journal=Genomics |volume=40 |issue= 1 |pages= 200–2 |year= 1997 |pmid= 9070946 |doi= 10.1006/geno.1996.4511 |name-list-format=vanc| author2=Blin N  | author3=Hilgert K  | display-authors=3  | last4=Seifert  | first4=Markus  | last5=Theisinger  | first5=Birgit  | last6=Engel  | first6=Matthias  | last7=Dooley  | first7=Steven  | last8=Zang  | first8=Klaus-Dieter  | last9=Welter  | first9=Cornelius }}
*{{cite journal  | author=Gött P, Beck S, Machado JC, ''et al.'' |title=Human trefoil peptides: genomic structure in 21q22.3 and coordinated expression. |journal=Eur. J. Hum. Genet. |volume=4 |issue= 6 |pages= 308-15 |year= 1997 |pmid= 9043862 |doi=  }}
*{{cite journal  | author=Tan XD |title=Intestinal trefoil factor binds to intestinal epithelial cells and induces nitric oxide production: priming and enhancing effects of mucin |journal=Biochem. J. |volume=338 |issue=  3|pages= 745–51 |year= 1999 |pmid= 10051448 |doi=10.1042/0264-6021:3380745  | pmc=1220112  |name-list-format=vanc| author2=Liu QP  | author3=Hsueh W  | display-authors=3  | last4=Chen  | first4=Yi-Hua  | last5=Chang  | first5=Hong  | last6=Gonzalez-Crussi  | first6=Frank  }}
*{{cite journal  | author=Seib T, Blin N, Hilgert K, ''et al.'' |title=The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3. |journal=Genomics |volume=40 |issue= 1 |pages= 200-2 |year= 1997 |pmid= 9070946 |doi= 10.1006/geno.1996.4511 }}
*{{cite journal  | author=Hattori M |title=The DNA sequence of human chromosome 21 |journal=Nature |volume=405 |issue= 6784 |pages= 311–9 |year= 2000 |pmid= 10830953 |doi= 10.1038/35012518  |name-list-format=vanc| author2=Fujiyama A  | author3=Taylor TD  | display-authors=3  | last4=Taylor  | first4=T. D.  | last5=Watanabe  | first5=H.  | last6=Yada  | first6=T.  | last7=Park  | first7=H.-S.  | last8=Toyoda  | first8=A.  | last9=Ishii  | first9=K. }}
*{{cite journal | author=Tan XD, Liu QP, Hsueh W, ''et al.'' |title=Intestinal trefoil factor binds to intestinal epithelial cells and induces nitric oxide production: priming and enhancing effects of mucin. |journal=Biochem. J. |volume=338 ( Pt 3) |issue=  |pages= 745-51 |year= 1999 |pmid= 10051448 |doi=  }}
*{{cite journal  | author=Berry A |title=Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region |journal=Genomics |volume=68 |issue= 1 |pages= 22–9 |year= 2001 |pmid= 10950923 |doi= 10.1006/geno.2000.6253  |name-list-format=vanc| author2=Scott HS  | author3=Kudoh J  | display-authors=3  | last4=Talior  | first4=Ilana  | last5=Korostishevsky  | first5=Michael  | last6=Wattenhofer  | first6=Marie  | last7=Guipponi  | first7=Michel  | last8=Barras  | first8=Christine  | last9=Rossier  | first9=Colette }}
*{{cite journal  | author=Hattori M, Fujiyama A, Taylor TD, ''et al.'' |title=The DNA sequence of human chromosome 21. |journal=Nature |volume=405 |issue= 6784 |pages= 311-9 |year= 2000 |pmid= 10830953 |doi= 10.1038/35012518 }}
*{{cite journal  | author=Wiede A |title=Synthesis and localization of the mucin-associated TFF-peptides in the human uterus |journal=Cell Tissue Res. |volume=303 |issue= 1 |pages= 109–15 |year= 2001 |pmid= 11235998 |doi=10.1007/s004410000297  |name-list-format=vanc| author2=Hinz M  | author3=Canzler E  | display-authors=3  | last4=Franke  | first4=Kornelia  | last5=Quednow  | first5=Claudia  | last6=Hoffmann  | first6=Werner  }}
*{{cite journal  | author=Berry A, Scott HS, Kudoh J, ''et al.'' |title=Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region. |journal=Genomics |volume=68 |issue= 1 |pages= 22-9 |year= 2001 |pmid= 10950923 |doi= 10.1006/geno.2000.6253 }}
*{{cite journal  | author=Yamachika T |title=Intestinal trefoil factor: a marker of poor prognosis in gastric carcinoma |journal=Clin. Cancer Res. |volume=8 |issue= 5 |pages= 1092–9 |year= 2002 |pmid= 12006524 |doi=  |name-list-format=vanc| author2=Werther JL  | author3=Bodian C  | display-authors=3  | last4=Babyatsky  | first4=M  | last5=Tatematsu  | first5=M  | last6=Yamamura  | first6=Y  | last7=Chen  | first7=A  | last8=Itzkowitz  | first8=S  }}
*{{cite journal | author=Wiede A, Hinz M, Canzler E, ''et al.'' |title=Synthesis and localization of the mucin-associated TFF-peptides in the human uterus. |journal=Cell Tissue Res. |volume=303 |issue= 1 |pages= 109-15 |year= 2001 |pmid= 11235998 |doi=  }}
*{{cite journal  | author=Kimura Y |title=Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis |journal=Hepatology |volume=36 |issue= 5 |pages= 1227–35 |year= 2002 |pmid= 12395334 |doi= 10.1053/jhep.2002.36157  |name-list-format=vanc| author2=Leung PS  | author3=Kenny TP  | display-authors=3  | last4=Van De Water  | first4=J  | last5=Nishioka  | first5=M  | last6=Giraud  | first6=AS  | last7=Neuberger  | first7=J  | last8=Benson  | first8=G  | last9=Kaul  | first9=R }}
*{{cite journal  | author=Yamachika T, Werther JL, Bodian C, ''et al.'' |title=Intestinal trefoil factor: a marker of poor prognosis in gastric carcinoma. |journal=Clin. Cancer Res. |volume=8 |issue= 5 |pages= 1092-9 |year= 2002 |pmid= 12006524 |doi=  }}
 
*{{cite journal  | author=Kimura Y, Leung PS, Kenny TP, ''et al.'' |title=Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis. |journal=Hepatology |volume=36 |issue= 5 |pages= 1227-35 |year= 2002 |pmid= 12395334 |doi= 10.1053/jhep.2002.36157 }}
}}
{{refend}}
{{refend}}


{{gene-21-stub}}
{{PDB Gallery|geneid=7033}}

Revision as of 05:26, 17 September 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Trefoil factor 3 is a protein that in humans is encoded by the TFF3 gene.[1][2][3]

Function

Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfide bonds. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. This gene is a marker of columnar epithelium and is expressed in a variety of tissues including goblet cells of the intestines and colon. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.[3]

In breast milk

Trefoil factors (TFF) are secretory products of mucin producing cells. They play a key role in the maintenance of the surface integrity of oral mucosa and enhance healing of the gastrointestinal mucosa by a process called restitution. TFF comprises the gastric peptides (TFF1), spasmolytic peptide (TFF2), and the intestinal trefoil factor (TFF3, this protein). They have an important and necessary role in epithelial restitution within the gastrointestinal tract. Significant amounts of TFF are present in human milk. Evidence has been presented that TFF3 isolated from milk strongly correlates with downregulation of IL-6 and IL-8 in human intestinal epithelial cells. On the other hand, TFF3 activated the epithelial cells in culture to produce beta defensins 2 (hBD2) and beta defensins 4 (hBD4). These findings suggest that TFF can activate intestinal epithelial cells and could actively participate in the immune system of breastfed babies by inducing the production of peptides related to innate defence, such as defensins.[4]

Activation of PAR-2 receptors

Two main mechanisms have been described for the activation of PAR-2: (A) by specifi c cleavage that unmask the receptor-activating peptide sequence present in the extracellular N-terminal domain of each PAR, leading to cell signaling via interaction of the exposed tethered ligand with the body of the receptor itself; and (B) by synthetic peptides, such as SLIGKV, that bind to the receptor, mimicking the actions of agonist proteases.[5] During lactation, TFF3 secreted in human milk may activate intestinal epithelial cells through PAR-2 receptors, which in turn induces hBD2 and hBD4 expression and cytokine regulation.[5]

Clinical significance

Using TFF3 as a marker of columnar epithelium, a process using an ingestible oesophageal sampling device (Cytosponge) coupled with immunocytochemistry for trefoil factor 3 to improve the accuracy and acceptability of the detection/screening of Barrett's oesophagus has been developed.[6] However the clinical utility of such a test may be limited by frequent staining of TFF3 in gastric cardia and subsequent risk of false positives.[7]

References

  1. ↑ Thim L, Woldike HF, Nielsen PF, Christensen M, Lynch-Devaney K, Podolsky DK (May 1995). "Characterization of human and rat intestinal trefoil factor produced in yeast". Biochemistry. 34 (14): 4757–64. doi:10.1021/bi00014a033. PMID 7718582.
  2. ↑ Gott P, Beck S, Machado JC, Carneiro F, Schmitt H, Blin N (May 1997). "Human trefoil peptides: genomic structure in 21q22.3 and coordinated expression". Eur J Hum Genet. 4 (6): 308–15. PMID 9043862.
  3. ↑ 3.0 3.1 "Entrez Gene: TFF3 trefoil factor 3 (intestinal)".
  4. ↑ Barrera GJ, Sanchez G, Gonzalez JE (November 2012). "Trefoil factor 3 isolated from human breast milk downregulates cytokines (IL8 and IL6) and promotes human beta defensin (hBD2 and hBD4) expression in intestinal epithelial cells HT-29". Bosn J Basic Med Sci. 12 (4): 256–64. PMC 4362502. PMID 23198942.
  5. ↑ 5.0 5.1 Barrera GJ, Tortolero GS (2016). "Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins". Bratislavské LekáRske Listy. 117 (6): 332–9. doi:10.4149/bll_2016_066. PMID 27546365.
  6. ↑ Kadri SR, Lao-Sirieix P, O'Donovan M, Debiram I, Das M, Blazeby JM, Emery J, Boussioutas A, Morris H, Walter FM, Pharoah P, Hardwick RH, Fitzgerald RC (2010). "Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study". BMJ. 341: c4372. doi:10.1136/bmj.c4372. PMC 2938899. PMID 20833740.
  7. ↑ Peitz U, Kouznetsova I, Wex T, Gebert I, Vieth M, Roessner A, Hoffmann W, Malfertheiner P (2004). "TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD)". Peptides. 25 (5): 771–7. doi:10.1016/j.peptides.2004.01.018. PMID 15177871.

Further reading

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