Faculty of Pharmacy, Lj. (FFALJ)
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Vloga monocitov in poškodbe DNA v vnetnih procesih pri bolnikih s sistemsko sklerozo ter vpletenost adiponektina in resolvina v razvoj fibroze = The role of monocytes and DNA damage in inflammation of patients with systematic sclerosis and involvement of adiponectina and resolvin in fibrotic development : doktorska disertacijaBrezovec, NežaSistemska skleroza (SSc) je sistemska avtoimunska revmatska bolezen, katere patogeneza ni popolnoma razjasnjena, tudi obvladovanje glavnih kliničnih znakov, kot sta vnetje in fibroza, s ... farmakoterapijo pogosto ni učinkovito. Z namenom boljšega razumevanja patogeneze in odkrivanja novih terapevtskih učinkovin smo proučevali oksidativni stres in migracijo monocitov pri bolnikih s SSc ter učinke adiponektina in resolvina D1 na vnetje in fibrozo. Metodološki pristop je zajemal delo na vzorcih bolnikov s SSc in zdravih oseb, celičnih kulturah in živalskem modelu. Pri bolnikih s SSc smo izmerili povišan indeks oksidativnega stresa (na osnovi povišanih serumskih reaktivnih kisikovih metabolitov in/ali antioksidantne kapacitete), več prelomov DNA v levkocitih ter oslabljene popravljalne mehanizme poškodb DNA. Na površini monocitov bolnikov s SSc smo dokazali povečano izražanje adhezijske molekule CD62L, katere izražanje je bilo spodbujeno s komponentami seruma bolnikov. Spremembe v oksidativnem stanju in migratornem fenotipu monocitov so pri bolnikih s SSc sovpadale s pljučno prizadetostjo, prisotnostjo avtoprotiteles in uporabo farmakoterapije. Na skeletnomišičnih celicah in skeletnomišičnih fibroblastih smo pokazali, da se adiponektin vpleta v vnetje in mišično regeneracijo z aktivacijo znotrajceličnih signalnih poti ter s spodbujanjem izločanja interlevkina-6 in sfingozin-1-fosfata, kot možne posledice povečane ceramidazne aktivnosti adiponektinskih receptorjev. AdipoRon, analog adiponektina, primerljivih učinkov ni izkazal. Resolvin D1 je na mišjem modelu peritonealne fibroze znižal delež polimorfonuklearnih celic v sistemskem krvnem obtoku, medtem ko vpliva na lokalno vnetje in fibrozo v trebušni steni ni imel. Negativno je vplival na izražanje hemerina, regulatorja vnetnih procesov, ki se veže na isti receptor kot resolvin E1. V doktorski disertaciji smo pokazali, kako obsežnejše stanje oksidativnega stresa in večji potencial migracije monocitov pri SSc sovpada s klinično sliko bolezni ter tako pripomogli k boljšemu razumevanju patogeneze. Obenem smo dokazali, da ima adiponektin učinke na mišično vnetje in regeneracijo, resolvin D1 pa potencial obvladovanja vnetja v fibrotičnih boleznih tudi z regulacijo izražanja ligandov resolvinskih receptorjev.Type of material - dissertation ; adult, seriousPublication and manufacture - Ljubljana : [N. Brezovec], 2023Language - slovenian, englishCOBISS.SI-ID - 146318339
Author
Brezovec, Neža
Other authors
Čučnik, Saša |
Lakota, Katja
Topics
Oksidativni stres |
Vnetje |
sistemska skleroza |
fibroza |
monociti |
poškodbe DNA |
adiponektin |
AdipoRon |
resolvin D1
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Author | Brezovec, Neža |
Title | Vloga monocitov in poškodbe DNA v vnetnih procesih pri bolnikih s sistemsko sklerozo ter vpletenost adiponektina in resolvina v razvoj fibroze = The role of monocytes and DNA damage in inflammation of patients with systematic sclerosis and involvement of adiponectina and resolvin in fibrotic development : doktorska disertacija |
Publication date | |
COBISS.SI-ID | 146318339 |
Publication version in repository | Publisher's version |
Publication licence | Unidentified |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
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Sistemske avtoimunske bolezni | P3-0314-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
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Knjižnica dr 0000000616 BREZOVEC NEŽA Vloga 0000000360 IN: 0017639 Knjižnica dr 616 BREZOVEC NEŽA Vloga 360 IN: 0017639 |
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Brezovec, Neža | 52564 |
Čučnik, Saša | 16362 |
Lakota, Katja | 28845 |
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