Title Ekspresija proteina u tkivima oboljelih od Dupuytrenove kontrakture : doktorska disertacija Author Davor Jurišić Mentor Miljenko Uravić (mentor)Committee member Zdenko Stanec (član povjerenstva)Committee member Željko Jeričević (član povjerenstva)Committee member Miljenko Kapović (član povjerenstva)Committee member Miljenko Uravić (član povjerenstva)Granter University of Rijeka Defense date and country 2009-03-06, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract U ovoj studiji je istražen status ekspresije ukupnih proteina u tkivima oboljelih od Dupuytrenove kontrakture, palmarne fibromatoze, uz pomoć metoda proteomike s ciljem utvrđivanja čimbenika uključenih u patogenezu ove bolesti. U istraživanju su korišteni uzorci tkiva pacijenata sa dijagnosticiranim zadnjim, involucijskim stadijem bolesti. Uspoređena je ekspresija proteina u promijenjenom tkivu čvorova i snopova s ekspresijom proteina u kontrolnim uzorcima tkiva dobivenih iz makroskopski
... More nezahvaćenog dijela palmarnog fascijalnog kompleksa. Za proteomsko profiliranje tkiva pacijenata korištena je metoda dvodimenzionalne gel-elektroforeze u kombinaciji s masenom spektrometrijom za identifikaciju proteina. Dobiveni su rezultati analizirani kombinacijom pretraživanja literature i bioinformatičkog pristupa. U svrhu bioinformatičke obrade korišteni su dinamički pretraživači mapa interaktoma čovjeka, HiMAP i STRING uz pomoć kojeg je izrađen „interkatom“. Potvrda rezultata bioinformatičke analize provedena je uz pomoć metode Western blot. Proteomsko profiliranje tkiva pacijenata oboljelih od Dupyutrenove kontrakture pokazalo je kako se u palmarnoj fasciji pacijenata u usporedbi s normalnim tkivom nalaze četrdeset i četiri pojačano eksprimirana proteina koji su uključeni u unutar- i izvan-staničnu signalizaciju, proliferaciju i diferencijaciju stanice, stanični metabolizam i oksidativni stres. Uz pomoć „interaktoma“ utvrđena je uloga signalnog proteina Akt te dvaju staničnih receptora, ERBB2 i IGF-1R, u progresiji Dupuytrenove kontrakture. Signalni put PI-3K/Akt mogao bi biti centralni događaj u razvoju Dupuytrenove kontrakture čiji simptomi direktno koreliraju sa promijenama citoskeletnih proteina, a koje su također utvrđene u ovom istraživanju. Na temelju dobivenih rezultata može se zaključiti kako su oksidativni stres, autokrina deregulacija i aktivacija signalnog puta PI-3K/Akt izuzetno važni čimbenici u razvoju Dupuytrenove kontrakture. Less Abstract (english) This doctoral thesis was aimed to study the total protein expression in patients' tissue affected by Dupuytren’s contracture and palmar fibromatosis by using proteomics methods. The aim was to determine possible molecular players involved in the pathogenesis of this disease. The tissue samples used for proteomic profiling were obtained from patients who have been diagnosed the last, involutional stage of the disease. The protein expression pattern in modified nod and bundle tissue was
... More compared with the protein expression pattern in control tissue samples obtained from macroscopically non-affected part of the palmar fascial complex. The proteomic tissue profiling was perfomed by using two-dimensional gel electrophoresis combined with mass spectrometry for protein identification. The obtained results were analyzed through data mining in combination with the bioinformatics. Bioinformatics analysis was performed by employing dynamic browsers for human protein-protein interaction map, HiMAP and STRING, and resulted as a predicted ’’interactome“ map. The confirmation of the bioinformatics analysis has been carried out by Western blot method. Proteomic tissue profiling in patients with Dupyutren’s contracture has shown that, unlike in normal tissue, the palmar fascia of patients has 44 differentially highly expressed proteins involved in intracellular and extracellular cell signalization, proliferation and differentiation, cellular metabolism and oxidative stress. The predicted ’’interactome“ has also proved useful in determining the role of the signaling protein Akt and two cellular receptors, ERBB2 and IGF-1R, in Dupuytren’s contracture progression. According to the obtained results, the PI-3K/Akt signalling pathway may be a croassroad of processes that lead to the development of Dupuytren’s contracture and ultimately to typical disease symptoms which directly correlates with cytoskeletal proteins’ modifications observed in this study. Based on the obtained results, it is plausible to believe that oxidative stress, autocrine deregulation and activation of the PI-3K/Akt signal pathway are important molecular factors in the development Dupuytren’s contracture. Less Keywords
Dupuytrenova kontraktura
dvodimenzionalna gel- elektroforeza
masena spektrometrija
bioinformatika
proteom
Keywords (english)
Dupuytren's contracture
Two-dimensional gel electrophoresis
Mass spectrometry
Bioinformatics
Proteome
Language croatian URN:NBN urn:nbn:hr:188:025748 Study programme Title: Biomedicine Postgraduate (doctoral) study programme Catalog URL http://libraries.uniri.hr/cgi-bin/ucat/unilib.cgi?form=D1120228012 Type of resource Text Extent 108 str; 30 cm File origin Born digital Access conditions Closed access Terms of use Created on 2017-01-19 19:13:04
