Uloga proteina obitelji GLI u diferencijaciji stanica trofoblasta

master's thesis

• Title (english): The role of GLI protein family in trophoblast cell differentiation
• Author: Anamarija Potkonjak
• Mentor: Ljiljana Šerman (mentor)
• Committee member: Nives Pećina-Šlaus (predsjednik povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Biochemistry

Abstract

GLI proteini sudionici su evolucijski konzerviranog Hedgehog (Hh) signalnog puta koji tijekom embrionalnog razvoja ima ključnu ulogu u prolifereciji i diferencijaciji stanica te morfogenezi određenih tkiva i organa. Hh signalni put aktivira se vezanjem Hh liganada za PTCH transmembranski receptor pri čemu se aktivira SMO te dolazi do povećane aktivnosti GLI transkripcijskih faktora koji potiču transkripciju ciljnih gena. Kod ljudi su pronađene tri izoforme GLI proteina GLI1, GLI2 i GLI3 koji zbog razlika u građi nemaju jednaku funkciju.
GLI proteini sudjeluju u diferencijaciji trofoblasta tijekom razvoja posteljice pri čemu se matične pluripotentne stanica trofoblasta diferenciraju u stanice citotrofoblasta koje su ključne u nastanku dvaju slojeva posteljice, nemigrirajućeg viloznog trofoblasta građenog od stanica sinciciotrofoblasta i invazivnog ekstraviloznog trofoblasta građenog od stanica citotrofoblasta. Ova dva sloja posteljice razlikuju se po svojim funkcijama. Ako dođe do poremećene aktivacije Hh signalnog puta i ometanja normalne signalne kaskade pa samim time i aberantne ekspresije GLI proteina, može doći do poremećaja u diferencijaciji trofoblasta što vodi razvoju raznih bolesti kao što su hidatiformna mola, invazivna mola, koriokarcinom, trofoblastični tumor ležišta posteljice i epiteloidni trofoblastični tumor. Navedene bolesti obilježene su abnormalnom proliferacijom trofoblasta te zajedno čine skup patoloških stanja posteljice zvan gestacijska trofoblastična bolest. Povezanost aberantne ekspresije GLI proteina s razvojem bolesti ukazuje na važnost pravilne regulacije ovih transkripcijskih faktora tijekom diferencijacije trofoblasta i normalnog razvoja posteljice.

Abstract (english)

GLI proteins are participants of the evolutionary conserved Hedgehog (Hh) signaling pathway, which plays a key role in the proliferation and differentiation of cells and morphogenesis of particular tissues and organs. Hh signaling pathways activate by binding of Hh ligands to the PTCH transmembranous receptor. In this process SMO activates and that leads to an increased activity of the GLI transcription factors, which support the transcription of target genes. There are three isoforms of the GLI proteins in people GLI1, GLI2, GLI3, which do not have the same function because of the difference in structure.
GLI proteins participate in the differentiation of trophoblasts in the development of the placenta. The stem cells of the trophoblast differentiate into cytotrophoblast cells (which play a key role in the creation of the two layers of the placenta), non-migratory villous trophoblast (built of syntitiotrophoblast cells) and an invasive extravillous trophoblast (built of cytotrophoblast cells). These two layers of the placenta differentiate in functions. If a disrupted activation of the Hh signaling pathway and disruption of a normal signaling cascade (and therefore even an aberrant expression of GLI proteins) occurs, a disruption in differentiation of the trophoblasts that leads to different diseases (such as hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour and epitheloid trophoblastic tumour) may occur. The mentioned diseases are characterised by abnormal proliferation of trophoblasts and together make up a group of pathological conditions known as gestational trophoblastic diseases. The connection of the aberrant expression of the GLI proteins along with the development of diseases shows the importance of a standard regulation of transcription factors during the dfferentiation of trophoblasts and a normal development of the placenta.

• Keywords: GLI proteini; diferencijacija trofoblasta; gestacijska trofoblastična bolest
• Keywords (english): GLI proteins; differentiation of trophoblasts; gestational trophoblastic diseases
• Language: croatian
• URN:NBN: urn:nbn:hr:105:095106
• 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: 2020-02-10 17:08:27