Uloga signalnog puta WNT u epitelno-mezenhimskoj tranziciji

master's thesis

• Title (english): Role of WNT signaling pathway in epithelial-mesenchymal transition
• Author: Vjekoslav Batarilo
• Mentor: Tamara Nikuševa Martić (mentor)
• Committee member: Frane Paić (predsjednik povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2017-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Medical Microbiology

Abstract

Epitelno-mezenhimska tranzicija je složeni molekularni proces u kojem dolazi do tranzicije epitelnih stanica u mezenhimske stanice. Stanične promjene koje se događaju tijekom EMT su brojne, a posljedica su prestanka ekspresije gena koji reguliraju epitelni fenotip te preuzimanja transkripcijskog obrasca ekspresije gena koji upravljaju mezenhimskim fenotipom. Neke od tih promjena su prestanak ekspresije E-kadherina, gubitak intercelularnih veza i apikalno-bazolateralne orijentacije stanice itd. Mezenhimske osobine koje stanice stječu su izgled nalik miofibroblastima, pokretljivost i invazivnost, stanice počinju secernirati molekule ekstracelularnog matriksa, manje su podložne aktivaciji apoptoze itd. EMT prisutna je i u fiziološkim i u patofiziološkim procesima. Fiziološki procesi koji su u najvećoj mjeri posljedica EMT su embriogeneza i reparacija tkiva, a patofiziološki procesi u kojima EMT sudjeluju su fibrogeneza i tumorigeneza. Jedan od glavnih puteva koji su zaslužni za aktivaciju ovog staničnog programa je Wnt signalni put. To je evolucijski drevni, konzervirani put. Kategorizirana su tri glavna Wnt puta: jedan kanonski i dva nekanonska. Kod ljudi postoji 19 različitih Wnt proteina, koji su kategorizirani zbog sličnost cisteinskih ostataka na N-terminalnom kraju, a ne prema funkcijama, koje su nota bene, vrlo različite. Wnt ligand veže se za Frizzled receptore te je središnja molekula β-katenin zaslužna za biološke učinke koji se pripisuju Wnt putu. β-katenin translocira se u jezgru gdje se veže za Tcf/Lef transkripcijski faktor i potiče ekspresiju ciljnih gena.

Abstract (english)

Epithelial-mesenchymal transition is a complex molecular process in which epithelial cells transform to mesenchymal cells. Cell changes that occur during EMT are numerous due to loss of epithelial gene expression, and activation of mesenchymal gene expression. Some of those changes are downregulation of E-cadherin expression, loss of epithelial adherens junctions, loss of apical-basolateral polarity etc. Mesenchymal traits which these cells acquire are myofibroblast-like shape, motility and invasiveness, secretion of extracellular matrix, increased resistance to apoptosis etc. EMT occurs both during physiological and pathophysiological processes. Physiological processes, which are to the greatest extent consequence of EMT, are embriogenesis and tissue reparation, while pathophysiological processes in which EMT has role are fibrogenesis and tumorigenesis. One of the major signaling pathway that activates EMT is Wnt signaling pathway. It is evolutionarily ancient and conserved pathway. There are three main Wnt signaling pathway branches; a canonical Wnt pathway and two non-canonical Wnt pathways. There are nineteen distinctive Wnt proteins in humans, which are classified as Wnt based on similarity of their N-terminal cysteine residues, rather than their functions which are quite different. The Wnt ligands bind to Frizzled receptors, while the central molecule β-catenin is responsible for biological effects of Wnt pathway. β-catenin translocates to the nucleus where it binds to Tcf/Lef transcription factor and upregulates expression of target genes.

• Keywords: epitelno-mezenhimska tranzicija; Wnt signalni put; genska ekspresija
• Keywords (english): epithelial-mesenchymal transition; Wnt signaling pathway; gene expression
• Language: croatian
• URN:NBN: urn:nbn:hr:105:910422
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-11-23 11:17:05