Uloga signalnog puta TGFbeta u regulaciji sustava urokinaznog plazminogenskog aktivatora

master's thesis

• Title (english): The role of the TGFbeta signaling pathway in regulation of urokinase plasminogen activator system
• Author: Dominik Puljić
• Mentor: Maja Matulić (mentor)
• Committee member: Maja Matulić (predsjednik povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Tomislav Ivanković (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Urokinazni plazminogenski aktivator izvanstanična je proteaza koja sudjeluje u procesima razgradnje izvanstaničnog matriksa te može biti regulirana sustavom koji upravlja procesima epitelno-mezenhimske tranzicije. Procesi tranzicije često su regulirani putem TGFβ koji potiče ekspresiju gena tipičnih za mezenhimski fenotip, kao i migraciju. Cilj ovog istraživanja bio je utvrditi ulogu signalnog puta TGFβ u regulaciji sustava urokinaznog plazminogenskog aktivatora (uPA) i u mehanizmu djelovanja natrijevog salicilata na promjenu aktivnosti uPA kod nekoliko staničnih linija tumora. Uzgojene su stanice glioblastoma transficirane plazmidom sa sekvencom za TGFβ koje su imale veću aktivnost urokinaze u odnosu na roditeljske, brže su migrirale, ali su im stopa proliferacije i morfologija bile nepromijenjene. Analizom proteina nije detektirano povećanje ekspresije urokinaze, ali jest njenog inhibitora. Inhibicija receptora TGFβ smanjila je bazalnu aktivnost urokinaze glioblastomskih stanica, kao i aktivnost induciranu obradom natrijevim salicilatom. Kod drugih dviju staničnih linija inhibicija puta TGFβ nije smanjila aktivnost urokinaze. Zaključeno je da TGFβ može sudjelovati u regulaciji sustava urokinaze, na stanično specifičan način.

Abstract (english)

Urokinase plasminogen activator is an extracellular protease involved in the processes of extracellular matrix remodelling which is supposed to be regulated by mechanism of epithelial-mesenchymal transition. These processes can be regulated by TGFβ which induce expression of genes typical for mesenchymal phenotype, as well as migration. The aim of this investigation was to establish the role of TGFβ signalling pathway in urokinase plasminogen activator (uPA) system regulation and in the mechanism of uPA activity changes caused by sodium salicylate in several tumour cell lines. We analysed glioblastoma cells transfected with plasmid containing TGFβ sequence and found higher urokinase activity and increased migration in comparison with parental cells, but proliferation rate and morphology were unchanged. Protein analysis did not reveal increase in urokinase expression but plasminogen inhibitor expression was upregulated. TGFβ receptor inhibition decreased the basal urokinase activity in glioblastoma cells, as well as activity induced by sodium salicylate treatment. In two other cell lines TGFβ signalling inhibition did not decrease urokinase activity. It was concluded that TGFβ can participate in urokinase system regulation, but in a cell specific way.

• Keywords: TGFβ; urokinazni plazminogenski aktivator; epitelno-mezenhimska tranzicija; natrijev salicilat
• Keywords (english): TGFβ; urokinase plasminogen activator; epithelial-mezenchymal transition; sodium salicylate
• Language: croatian
• URN:NBN: urn:nbn:hr:217:200670
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2020-09-27
• Created on: 2018-10-29 12:21:49