Uporaba javno dostopnih podatkovnih zbirk in bioinformatičnih orodij za analizo genskega izražanja pri sistemski sklerozi

Mrak Poljšak, Katjuša

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Title:	Uporaba javno dostopnih podatkovnih zbirk in bioinformatičnih orodij za analizo genskega izražanja pri sistemski sklerozi
Authors:	ID Mrak Poljšak, Katjuša (Author) ID Potočnik, Uroš (Mentor) More about this mentor... ID Lakota, Katja (Comentor)
Files:	MAG_Mrak_Poljsak_Katjusa_2019.pdf (5,33 MB) MD5: 7C527EF022ECC30D9D379F2A66A5F981 PID: 20.500.12556/dkum/9ef82cff-93f0-4fdd-9291-7fafd2ec827e
Language:	Slovenian
Work type:	Master's thesis/paper
Typology:	2.09 - Master's Thesis
Organization:	FZV - Faculty of Health Sciences
Abstract:	Izhodišča: Sistemska skleroza (SSc) je kronična sistemska avtoimunska bolezen vezivnega tkiva. Patogeneza bolezni še ni popolnoma poznana. Pogost vzrok smrti pri bolnikih s SSc je intersticijska pljučna bolezen. Naš namen je bil z uporabo javno dostopnih podatkovnih baz in bioinformatičnih orodij ugotoviti značilen profil izražanja genov in vpletenost različnih celičnih tipov v razvoju fibroze pri bolnikih s SSc s pridruženo intersticijsko pljučno boleznijo (SSc-ILD). Raziskovalne metode: Za analizo podatkov genskega izražanja fibroblastov, izoliranih iz pljučnega tkiva, in celic celotnega pljučnega tkiva bolnikov smo uporabili program BRB-ArrayTools. V drugem delu smo s pomočjo bioinformatičnih orodij String in Reactome raziskali proteinske interakcije genov s spremenjenim izražanjem in jih analizirali glede na vpletenost v signalne poti. Rezultati: V analizi genskega izražanja pljučnih fibroblastov smo dokazali moteno regulacijo genov, vpletenih v procese fibroze. Z analizo pljučnega tkiva smo dokazali moteno regulacijo genov izvenceličnega matriksa, poti TGF-β in znižano izražanje citokinov, kemokinov in njihovih receptorjev. Ugotovili smo možne vplive različnih miRNA in transkripcijskih faktorjev družine NFkB, STAT in JUN na transkriptom fibroblastov ter vpliv PPAR in RAR na transkriptom celic pljučnega tkiva. Ugotovili smo epigenetski vpliv na celično proliferacijo, angiogenezo in izražanje signalne poti TGF-β prek hsa-miR-132 miRNA v celicah pljučnega tkiva. Diskusija in zaključek: Dokazali smo pomembno spremenjeno izražanje imunoglobulinov, kar kaže na pomembno vlogo celic B v pljučnem tkivu bolnikov v patogenezi bolezni, in ugotovili, da so geni, pomembno spremenjeni v fibroblastih, predvsem vpleteni v celično proliferacijo, geni drugih celic pljučnega tkiva pa so v veliki meri vključeni v mehanizme imunskega sistema in celične signalizacije, kar ponuja potencialne nove tarče za zdravljenje.
Keywords:	fibroza, fibroblasti, pljučno tkivo, imunski sistem, epigenetika.
Place of publishing:	Maribor
Publisher:	[K. Mrak Poljšak]
Year of publishing:	2019
PID:	20.500.12556/DKUM-73316
UDC:	575.112(043.2)
COBISS.SI-ID:	2493604
NUK URN:	URN:SI:UM:DK:MMNILRBA
Publication date in DKUM:	29.05.2019
Views:	1511
Downloads:	108
Metadata:
Categories:	FZV
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Licences

License:	CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Link:	http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:	The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:	25.03.2019

Secondary language

Language:	English
Title:	Analysis of gene expression using public data and bionformatic tools in systemic sclerosis
Abstract:	Starting points: Systemic sclerosis (SSc) is chronic, autoimmune connective tissue disease. Its pathogenesis is not completely understood. Major cause for mortality in this disease is interstitial lung disease (ILD). Our aim was to use publicly available databases and bioinformatic tools to discern gene expression and cell type involvement in development of fibrosis in SSc-ILD patients. Methods: We used BRB-Array tools for analysis of gene expression in lung tissue and fibroblasts isolated from lung tissue of SSc patient and control. Furthermore, String and Reactome bioinformatic tools were used to analyze protein interactions between genes with changed expression and analyze pathways involving these genes, to better understand major drivers of disease. Results: In analysis of gene expression we found perturbations in expression of genes leading to fibrosis such as extracellular matrix proteins, TGF-β signaling pathway, decreased levels of cytokines, chemokines and their receptors expression. Based on gene expression profile we found possible miRNA and NFkB family STAT and JUN transcription factor involvement to/on transcriptome of fibroblasts and PPAR and RAR transcription factors to/on transcriptome of lung tissue. We found hsa-miR-132 miRNA epigenetic influence/signature on cell proliferation, angiogenesis and TGF-β signaling pathway expression in lung tissue withouth fibroblasts. We found profound changes in imunoglobulin gene expression, which is implying important role of B cells in lung tissue of these patients. Discussion and conclusion: The genes with significantly changed expression in fibroblast were those involved in cell proliferation, while differentially expressed genes of other cell types in lung tissue were those belonging to immune system and cell signalization, which implicates possible new therapeutic approaches.
Keywords:	fibrosis, fibroblasts, lung tissue, immune system, epigenetics.

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