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doctoral thesis
Izraženost Wnt 4 u presađenim bubrezima
Zagreb: University of Zagreb, School of Medicine, 2019. urn:nbn:hr:105:047989
Mesar, Ines
University of Zagreb
School of Medicine

Cite this document

Mesar, I. (2019). Izraženost Wnt 4 u presađenim bubrezima (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:047989

Mesar, Ines. "Izraženost Wnt 4 u presađenim bubrezima ." Doctoral thesis, University of Zagreb, School of Medicine, 2019. https://urn.nsk.hr/urn:nbn:hr:105:047989

Mesar, Ines. "Izraženost Wnt 4 u presađenim bubrezima ." Doctoral thesis, University of Zagreb, School of Medicine, 2019. https://urn.nsk.hr/urn:nbn:hr:105:047989

Mesar, I. (2019). 'Izraženost Wnt 4 u presađenim bubrezima ', Doctoral thesis, University of Zagreb, School of Medicine, accessed 17 September 2024, https://urn.nsk.hr/urn:nbn:hr:105:047989

Mesar I. Izraženost Wnt 4 u presađenim bubrezima [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2019 [cited 2024 September 17] Available at: https://urn.nsk.hr/urn:nbn:hr:105:047989

I. Mesar, "Izraženost Wnt 4 u presađenim bubrezima ", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2019. Available at: https://urn.nsk.hr/urn:nbn:hr:105:047989

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Metadata
TitleIzraženost Wnt 4 u presađenim bubrezima
Title (english)Expression of Wnt 4 in transplant kidneys
AuthorInes Mesar
MentorNikolina Bašić Jukić (mentor)
Committee membernije dostupno (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2019-03-06, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Postupnim razvojem moderne medicine preživljenje i kvaliteta života oboljelih od bubrežnih bolesti se značajno popravlja. Velik dio presađenih bubrega se gubi zbog kroničnih promjena u parenhimu presatka za koji se pretpostavlja da su s jedne strane posljedica neželjenih učinaka imunosupresivnih lijekova, a s druge strane kasnih kroničnih imunoloških zbivanja. Obitelj Wnt (od eng. wingless-type MMTV integration site family) gena ima ključnu ulogu u embionalnom razvoju bubrega. Pretpostavljena je i njihova uloga tijekom života prilikom ozljede bubrega, te procesa oporavka od ozljede ili procesa fibroze. U dosadašnjim istraživanjima, nije jasna njihova uloga niti izraženost u transplantiranim bubrezima. Cilj ovog istraživanja je bio analizirati postoji li povećana izraženost Wnt 4 u presađenim u odnosu na zdrave bubrege, te razlikuje li se u odnosu na uzrok graftektomije. Pratili smo izraženost Wnt 4 u tkivu zdravih (nativnih) bubrega te u tkivu kiruški odstrajenih transplantiranih bubrega u ovisnosti o različitim čimbenicima, za koje smatramo da mogu imati utjecaja na njegovu izraženost. U istraživanje smo uključili 59 bolesnika kojima je zbog završnog stadija zatajenja bubrežne funkcije učinjena transplantacija bubrega s umrle osobe. Kao kontrolna skupina uzeti su uzorci zdravog tkiva bubrega, dobiveni nefrektomijom 24 bolesnika s lokaliziranim tumorom bubrega. Dobiveni rezultati nisu potvrdili našu hipotezu, već suprotno, temeljem naših rezultata možemo zaključiti da se u tkivu presađenih bubrega vrlo rano gubi izraženost Wnt 4 dok je u zdravom tkivu bubrega on prisutan i korelira sa starošću. Temeljem toga bi se mogla pretpostaviti njegova uloga u održavanju strukture i funkcije bubrega. Naše istraživanje je pokazalo kako trajanje hladne ishemije, čak i produženo, ne dovodi do značajnije kraćeg preživljenja presatka. Potvrđena je pojačana izraženost Wnt 4 kod produženog trajanja hladne ishemije, te njegova važnost kao vjerojatnog faktora u regeneraciji bubrežnog tkiva i posljedično tome preživljenja presatka. Prema našim rezultatima, a uvidom u dostupnu literaturu, ovo je prvi dokaz u ljudi o ulozi jače izraženosti Wnt 4 i boljem preživljenju bubrežnog presatka kao faktora regeneracije tkiva nakon perioda ishemije. To otvara čitavo područje istraživanja uvođenja moguće terapije Wnt agonista u liječenju ishemijske ozljede bubrega u transplantiranih bolesnika.
Abstract (english)
With the gradual development of modern medicine the overall survival and quality of life of patients with chronic kidney disease significantly improved. Kidney transplantation significantly enhanced the treatment of end-stage renal disease patients. However, many transplanted kidneys are lost due to chronic graft changes caused by immunosupression therapy or occurence of late chronic immunologic response. The family of Wnt (wingless- type MMTV integration site family) genes are constituted of 19, till now, described members. Some of this proteins are present in kidney development but also in the process of kidney injury and reparation. Due to this published results it is assumed that the same molecules responsible for the regulation of nephrogenesis also participates in the patophysiology of tubulointerstitial kidney disease. It is still not clear which Wnt gene is responsible for protection and which for damage especially in transplanted kidneys. The aim of this study was to analyze whether Wnt 4 expression is increased in transplanted kidneys compared to healthy kdiney samples and is it dependable of different causes of graftectomies. In this study we have included 59 kidney transplanted patients from deceased donors and 24 nephrectomized patients due to localised kidney tumours as a control group. The obtained results did not confirmed our hypothesis. On the contrary, the Wnt 4 expression was significantly lower in the kidney transplanted patients group compared to healthy kidney tissue samples which was strongly correlated with age. Although the Wnt 4 expression was correlated with higher age, its most independent and significant correlation was with longer cold ischemia time. This are, at least to our knowledge, the first results which reported higher Wnt 4 expression and better kidney graft survival and its possible role as an factor in kidney graft regeneration especially in prolonged ischemia time and acute tubular necrosis. These results emphasize the importance on future studies of different Wnt receptors agonists as a novel therapy in treating tissue ichemia injuries.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:047989
Study programmeTitle: Biomedicine and Health Sciences
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
Type of resourceText
Extent105 str.
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
RepositoryDr Med - University of Zagreb School of Medicine Digital Repository
Created on2023-05-05 08:33:34

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