{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:54:58Z","timestamp":1787169298382,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006588","name":"Ministarstvo Znanosti, Obrazovanja i Sporta","doi-asserted-by":"publisher","award":["219-0982914-2179"],"award-info":[{"award-number":["219-0982914-2179"]}],"id":[{"id":"10.13039\/501100006588","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Trefoil family factor (TFF) proteins contribute to antimicrobial defense and the maintenance of sinonasal epithelial barrier integrity. Dysregulation of TFF expression may be involved in the development of chronic inflammation and tissue remodeling characteristically found in chronic rhinosinusitis with nasal polyposis (CRSwNP). Expressions of TFF1 and TFF3 were determined in specimens of middle nasal turbinate (MNT-0), bulla ethmoidalis (BE), and nasal polyps (NP) from CRSwNP patients (n = 29) and inferior nasal turbinate from a group of control patients (underwent nasal septoplasty, n = 25). An additional MNT sample was collected 6 months after functional endoscopic sinus surgery (FESS, MNT-6). TFF1 mRNA levels were significantly reduced in all specimens by approximately three- to five-fold, while TFF3 was increased in MNT-0, as compared with controls. Six months after surgery their levels were reversed to control values. CRSwNP patients with S. epidermidis isolated from sinus swabs showed upregulation of TFF3 in MNT and NP as compared with patients with sterile swabs. Target gene regulation was not affected by the presence of type 2 inflammation in patients with confirmed allergy. Results of this study imply participation of TFFs genes in the development of CRSwNP.<\/jats:p>","DOI":"10.3390\/ijms20215461","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T12:30:50Z","timestamp":1572611450000},"page":"5461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis"],"prefix":"10.3390","volume":"20","author":[{"given":"Martina","family":"Mihalj","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, University Hospital Osijek, 31000 Osijek, Croatia"},{"name":"Department of Physiology and Immunology, Faculty of Medicine, University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maro","family":"Bujak","sequence":"additional","affiliation":[{"name":"Department of Materials Chemistry, Ru\u0111er Bo\u0161kovi\u0107 Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josip","family":"Butkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, University Hospital Osijek, 310000 Osijek, Croatia"},{"name":"Department of Otorhinolaryngology and Maxillofacial Surgery, Faculty of Medicine, University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Zub\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Maxillofacial Surgery, Faculty of Medicine, University of Osijek, 31000 Osijek, Croatia"},{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Osijek; 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-4926","authenticated-orcid":false,"given":"Maja","family":"Tolu\u0161i\u0107 Levak","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, University Hospital Osijek, 31000 Osijek, Croatia"},{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josip","family":"\u010ces","sequence":"additional","affiliation":[{"name":"Dental Centre \u010ces, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlatko","family":"Kopi\u0107","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, University Hospital Osijek, 310000 Osijek, Croatia"},{"name":"Department of Otorhinolaryngology and Maxillofacial Surgery, Faculty of Medicine, University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"Baus Lon\u010dar","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Ru\u0111er Bo\u0161kovi\u0107 Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrvoje","family":"Mihalj","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Maxillofacial Surgery, Faculty of Medicine, University of Osijek, 31000 Osijek, Croatia"},{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Osijek; 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhino12.000","article-title":"European position paper on rhinosinusitis and nasal polyps 2012","volume":"50","author":"Fokkens","year":"2012","journal-title":"Rhinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2500\/ajra.2011.25.3680","article-title":"Pathophysiology of chronic rhinosinusitis with nasal polyp","volume":"25","author":"Hsu","year":"2011","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00130832-200302000-00001","article-title":"Nasal polyposis: An update: Editorial review","volume":"3","author":"Pawankar","year":"2003","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2500\/108854196778662264","article-title":"Nasal polyps update. Histopathology","volume":"17","author":"Hellquist","year":"1996","journal-title":"Allergy Asthma Proc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrm1203","article-title":"Trefoil factors: Initiators of mucosal healing","volume":"4","author":"Taupin","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1007\/s00018-008-8646-5","article-title":"The trefoil factor family\u2014small peptides with multiple functionalities","volume":"66","author":"Kjellev","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0014-5793(89)80690-8","article-title":"A new family of growth factor-like peptides. \u201cTrefoil\u201d disulphide loop structures as a common feature in breast cancer associated peptide (pS2), pancreatic spasmolytic polypeptide (PSP), and frog skin peptides (spasmolysins)","volume":"250","author":"Thim","year":"1989","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1515\/bmc-2015-0020","article-title":"Trefoil factor family peptides--friends or foes?","volume":"6","author":"Busch","year":"2015","journal-title":"Biomol. Concepts"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/(SICI)1096-9896(200002)190:2<133::AID-PATH518>3.0.CO;2-B","article-title":"Trefoil factor family domain peptides in the human respiratory tract","volume":"190","author":"Ulrich","year":"2000","journal-title":"J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/alr.21334","article-title":"Chronic rhinosinusitis without nasal polyps is associated with increased expression of trefoil factor family peptides","volume":"4","author":"Li","year":"2014","journal-title":"Int. Forum. Allergy Rhinol."},{"key":"ref_11","first-page":"2541","article-title":"Expression of Clara cell 10-kDa protein and trefoil factor family 1 in patients with chronic rhinosinusitis and nasal polyps","volume":"15","author":"Wang","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev-physiol-021115-105447","article-title":"Trefoil Factor Peptides and Gastrointestinal Function","volume":"79","author":"Aihara","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1136\/gut.48.6.792","article-title":"Ulcer associated cell lineage glands expressing trefoil peptide genes are induced by chronic ulceration in ileal pouch mucosa","volume":"48","author":"Pera","year":"2001","journal-title":"Gut"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1172\/JCI3304","article-title":"The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor- and MAP kinase-dependent interregulation","volume":"103","author":"Taupin","year":"1999","journal-title":"J. Clin. Invest."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1007\/s00018-005-5480-x","article-title":"Multiple regulatory pathways for trefoil factor (TFF) genes","volume":"62","author":"Giraud","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1556\/1886.2015.00028","article-title":"TFF peptides play a role in the immune response following oral infection of mice with toxoplasma Gondii","volume":"5","author":"Fu","year":"2015","journal-title":"Eur. J. Microbiol. Immunol. (Bp)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1159\/000341463","article-title":"Increased susceptibility to Yersinia enterocolitica Infection of Tff2 deficient mice","volume":"30","author":"Shah","year":"2012","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1126\/science.274.5285.259","article-title":"Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein","volume":"274","author":"Lefebvre","year":"1996","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1007\/s00018-005-5483-7","article-title":"Trefoil factor family 2 deficiency and immune response","volume":"62","author":"Kayademir","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2932","DOI":"10.1007\/s00018-005-5481-9","article-title":"Trefoil factors TFF (trefoil factor family) peptide-triggered signals promoting mucosal restitution","volume":"62","author":"Hoffmann","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.tem.2007.10.003","article-title":"Are trefoil factors oncogenic?","volume":"19","author":"Perry","year":"2008","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jaip.2016.04.012","article-title":"Chronic Rhinosinusitis with Nasal Polyps","volume":"4","author":"Stevens","year":"2016","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_23","first-page":"169","article-title":"Nasal polyps in patients with rhinitis and asthma","volume":"23","author":"Grigoreas","year":"2002","journal-title":"Allergy Asthma Proc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s00405-018-4990-8","article-title":"Complications in septoplasty based on a large group of 5639 patients","volume":"275","author":"Gwizdalska","year":"2018","journal-title":"Eur. Arch Otorhinolaryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3389\/fcimb.2017.00090","article-title":"Host Response to staphylococcus epidermidis colonization and infections","volume":"7","author":"Nguyen","year":"2017","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/nm763","article-title":"Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice","volume":"8","author":"Tebbutt","year":"2002","journal-title":"Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1126\/science.274.5285.262","article-title":"Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor","volume":"274","author":"Mashimo","year":"1996","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1097\/00005537-199802000-00001","article-title":"Long-term results of functional endoscopic sinus surgery","volume":"108","author":"Senior","year":"1998","journal-title":"Laryngoscope"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"306","DOI":"10.5935\/1808-8694.20130055","article-title":"Long-term outcomes of endoscopic sinus surgery for chronic rhinosinusitis with and without nasal polyps","volume":"79","author":"Mascarenhas","year":"2013","journal-title":"Br. J. Otorhinolaryngol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"408","DOI":"10.4193\/Rhino11.221","article-title":"Expression of Trefoil factor family peptides in the nasal allergic mucosa","volume":"50","author":"Miyahara","year":"2012","journal-title":"Rhinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.2174\/092986707782023226","article-title":"TFF (trefoil factor family) peptides and their potential roles for differentiation processes during airway remodeling","volume":"14","author":"Hoffmann","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jaci.2009.10.072","article-title":"Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps","volume":"125","author":"Peters","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1007\/s11033-010-0036-z","article-title":"IL-6\/STAT3\/TFF3 signaling regulates human biliary epithelial cell migration and wound healing in vitro","volume":"37","author":"Jiang","year":"2010","journal-title":"Mol. Biol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0002-9440(10)63243-9","article-title":"Regulation and function of trefoil factor family 3 expression in the biliary tree","volume":"165","author":"Nozaki","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_35","first-page":"275","article-title":"Trefoil factor family 1 is involved in airway remodeling of mustard lung","volume":"15","author":"Nourani","year":"2016","journal-title":"Iran J. Allergy Asthma Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1369\/jhc.6A7100.2007","article-title":"Tissue localization of human trefoil factors 1, 2, and 3","volume":"55","author":"Madsen","year":"2007","journal-title":"J. Histochem. Cytochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vandesompele, J., de Preter, K., Pattyn, F., Poppe, B., van Roy, N., de Paepe, A., and Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome boil., 3.","DOI":"10.1186\/gb-2002-3-7-research0034"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:31:21Z","timestamp":1760189481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/21\/5461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,1]]},"references-count":38,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["ijms20215461"],"URL":"https:\/\/doi.org\/10.3390\/ijms20215461","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,1]]}}}