Приказ основних података о дисертацији

Expression of genes associated with inflammation and fibrosis and candidate genes for cell therapy optimization in patients with systemic sclerosis

dc.contributor.advisorSpasovski, Vesna
dc.contributor.otherPavlović, Sonja
dc.contributor.otherBrajušković, Goran
dc.contributor.otherDamjanov, Nemanja
dc.contributor.otherRadović, Svetlana
dc.creatorVreća, Miša
dc.date.accessioned2019-05-16T10:19:26Z
dc.date.available2019-05-16T10:19:26Z
dc.date.available2020-07-03T08:14:42Z
dc.date.issued2019-02-20
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/11032
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6773
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:19657/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025215922
dc.description.abstractSistemska skleroza (SSc) je retka, heterogena, multisistemska, autoimuna bolest nepoznate etiologije sa varijabilnim kliničkim manifestacijama i nepredvidivim i često letalnim ishodom. Osnovne karakteristike ove bolesti su poremećaji u imunom sistemu i inflamacija, vaskulopatija, preterana produkcija komponenti vanćelijskog matriksa i progresivna fibroza kože i unutrašnjih organa. Pronalaženje novih biomarkera, koji bi omogućili bolje razumevanje patogeneze same bolesti, bilo bi od presudne važnosti za ranije uspostavljanje dijagnoze, bolju klasifikaciju pacijenata i primenu adekvatnije terapije. Stoga je u okviru ove teze ispitana asocijacija odabranih genetičkih varijanti u genima IRAK1 i miRNK-146a sa predispozicijom za razvoj SSc. Takođe, u cilju otkrivanja potencijalno novih i pouzdanih biomarkera praćena je ekspresija odabranih učesnika signalnih puteva JAK2/STAT3 i NF-kB, uključenih u proces inflamacije na sistemskom i proces fibroze na lokalnom nivou. Upotreba ćelijske terapije u lečenju oštećenja malih zglobova kod ovih pacijenata jedan je od potencijalno novih terapeutskih pristupa. Uprkos rastućem znanju i upotrebi mezenhimskih matičnih ćelija izolovanih iz adopoznog tkiva (aMMĆ) u ćelijskoj terapiji, veoma malo se zna kako gajenje ovih ćelija u laboratorijskim uslovima utiče na njihovu sposobnost samoobnove i potencijal za diferencijaciju u hondrocite. U cilju ispitivanja uticaja dužine gajenja ćelija na njihovu sposobnost samoobnove i potencijala za hondrogenu diferencijaciju, praćena je ekspresija gena markera matičnosti i hondrogene diferencijacije tokom in vitro kultivacije ovih ćelija. Studija asocijacije odabranih genetičkih varijanti, IRAK1 rs3027898 C>A i miRNK-146a rs2910164 G>C izvedena je na grupi od 102 SSc pacijenata i 66 zdravih ispitanika, direktnim sekvenciranjem po Sangeru. Relativna kvantifikaciona analiza ekspresije gena IL6, JAK2, STAT3, TLR7, TLR9, IRAK1 i miRNK-146a u mononuklearnim ćelijama periferne krvi (MNĆPK), izvršena je na podgrupi od 50 SSc pacijenata i 13 zdravih ispitanika, dok je ekspresiona analiza odabranih gena na lokalnom nivou izvedena na uzorcima tkiva kože, sa i bez fibrotičnih promena, poreklom iz 5 SSc pacijenata...sr
dc.description.abstractSystemic sclerosis (SSc) is a rare heterogeneous, multisystem, autoimmune disease with unknown etiology, characterized with variable clinical manifestations, and unpredictable and often lethal outcome. The basic mechanism of the disease appears to involve aberrant immune activation and inflammation, vasculopathy, overproduction of extracellular matrix proteins and progressive fibrosis of skin and internal organs. The identification of novel biomarkers will not only enable a better understanding of the disease pathogenesis, but also contribute to earlier establishment of diagnosis, better classification of patients, and the application of more appropriate therapy. Therefore, within this thesis, it was examined the association of selected genetic variants in the IRAK1 and miRNA-146a genes with the predisposition for development of SSc. In order to discover potentially novel and reliable biomarkers, the expression of selected participants of JAK2/STAT3 and NF-kB signal pathways, involved in the process of inflammation at the systemic and process of fibrosis at the local level, was examined. Stem cell therapy, is one of the potential new therapeutic approaches in the treatment of small-joint damage in SSc patients. Despite growing knowledge and utilization of adipose tissue-derived mesenchymal stem cell (aMSC) in therapy, very little known about how prolonged cultivation of these cells in laboratory conditions affects their ability for self-renewal and their potential for differentiation into functional chondrocytes. In order to investigate the influence of the long-term ex vivo cultivation on their potency and potential for chondrogenic diferrentiation, the expression of genes, markers of stemness, as well as markers for chondrogenic differentiation, during prolonged in vitro aMSC cultivation, was investigated. The association study between selected genetic variants, IRAK1 rs3027898 C> A and miRNA-146a rs2910164 G> C, and susceptibility to SSc was performed on a group of 102 SSc patients and 66 healthy subjects, by Sanger sequencing. Relative quantification analysis of the IL6, JAK2, STAT3, TLR7, TLR9, IRAK1 and miRNA-146a gene expressions in peripheral blood mononuclear cells, were performed on a subgroup of 50 SSc patients and 13 healthy subjects, while the expression analyzes of selected genes at the local level were performed on skin tissue samples, with and without fibrotic changes, originating from 5 SSc patients...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/316088/EU//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41004/RS//
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectSistemska sklerozasr
dc.subjectSystemic sclerosisen
dc.subjectinflammationen
dc.subjectfibrosisen
dc.subjectgene expression analyzesen
dc.subjectbiomarkersen
dc.subjectsignal pathway JAK2/STAT3en
dc.subjectsignal pathway NF-kBen
dc.subjectaddipose tissue-derived MSCen
dc.subjectoptimization of cell therapyen
dc.subjectinflamacijasr
dc.subjectfibrozasr
dc.subjectbiomarkerisr
dc.subjectanaliza ekspresije genasr
dc.subjectsignalni put JAK2/STAT3sr
dc.subjectsignalni put NF-kBsr
dc.subjectmezenhimske matične ćelije izolovane iz adopoznog tkivasr
dc.subjectoptimizacija ćelijske terapijesr
dc.subjectaMMĆsr
dc.titleEkspresije gena markera inflamacije i fibroze i gena kandidata za optimizovanu ćelijsku terapiju kod pacijenata sa sistemskom sklerozomsr
dc.title.alternativeExpression of genes associated with inflammation and fibrosis and candidate genes for cell therapy optimization in patients with systemic sclerosisen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/3407/Disertacija.pdf
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/3408/IzvestajKomisije20045.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/3407/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/3408/IzvestajKomisije20045.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_11032


Документи за докторску дисертацију

Thumbnail
Thumbnail

Ова дисертација се појављује у следећим колекцијама

Приказ основних података о дисертацији