Utjecaj manoze i galaktoze na ekspresiju gena, kinetiku i proliferaciju mioblasta kod pacijenata s kongenitalnom mišićnom distrofijom

master's thesis

• Title (english): Effect of mannose and galactose on myoblast gene expression, kinetics and proliferation in congenital muscular dystrophy patients
• Author: Lucija Ćužić
• Mentor: Marija Zekušić (mentor)
• Mentor: Inga Urlić (komentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Petra Korać (član povjerenstva)
• Committee member: Tomislav Ivanković (član povjerenstva)
• Committee member: Petra Peharec Štefanić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2025-02-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Distroglikanopatija je tip kongenitalne mišićne distrofije uzrokovan gubitkom funkcije α-
distroglikana zbog nepravilne glikozilacije. Jedan od podtipova ove bolesti povezan je s
mutacijama u genu za enzim POMT2, ključnom za prijenos manoze na glikanski lanac α-
distroglikana. Prijašnja istraživanja pokazala su kako terapija određenim monosaharidima može
obnoviti glikozilaciju kod nekih tipova distroglikanopatija. Ovo istraživanje fokusiralo se na
učinke manoze i galaktoze na ekspresiju gena,... More kinetiku i proliferaciju mioblasta izoliranih iz
pacijenata s mutacijama u genu POMT2. Cilj istraživanja bio je na staničnoj kulturi mioblasta
izoliranih iz pacijenata s i bez mišićne distrofije provjeriti ima li tretman manozom i galaktozom
utjecaj na poboljšanje genske ekspresije α-distroglikana i smanjenje upalnog procesa mišićnih
vlakana te kinetiku, proliferaciju i vijabilnost mioblasta. Rezultati pokazuju kako su morfološke
karakteristike mioblasta od pacijenata s kongenitalnom mišićnom distrofijom te obrasci
ekspresije gena u njima značajno različite u usporedbi s kontrolnim mioblastima. Tretmani
manozom i galaktozom nisu doveli do značajnih promjena u ekspresiji gena. Praćenjem
kinetike i proliferacije mioblasta metodom fazno holografske mikroskopije utvrđen je smanjen
proliferacijski kapacitet i veća brzina kretanja mioblasta od pacijenata s kongenitalnom
mišićnom distrofijom u odnosu na kontrolne mioblaste, a tretmani šećerima djelomično su
modificirali ovaj učinak. Ovo istraživanje pruža uvide u kompleksnu prirodu
distroglikanopatija i potencijal monosaharida u budućim terapijskim pristupima. Less

Abstract (english)

Dystroglycanopathy is a type of congenital muscular dystrophy caused by the loss of function
of α-dystroglycan due to impaired glycosylation. One subtype of this disease is linked to
mutations in the POMT2 enzyme, which plays a crucial role in transferring mannose onto the
glycan chain of α-dystroglycan. Previous studies have shown that monosaccharide-based
therapies can restore glycosylation in certain types of dystroglycanopathies. This study
evaluates effects of mannose and galactose on... More gene expression, kinetics, and proliferation of
myoblasts derived from patients with POMT2 mutations. The aim of this research is to examine
whether treatment with mannose and galactose can enhance α-dystroglycan gene expression,
reduce inflammation in muscle fibers, and improve the kinetics, proliferation, and viability of
myoblasts in cell cultures from patients with and without muscular dystrophy. The results
revealed significant morphological differences and altered gene expression patterns in
myoblasts from patients with congenital muscular dystrophy compared to controls. Treatment
with mannose and galactose did not significantly affect gene expression. Digital holographic
microscopy analysis of cell kinetics and proliferation demonstrated reduced proliferation rates
and increased cell motility in congenital muscular dystrophy derived myoblasts, with
monosaccharide treatments partially modifying this effect. This research offers insights into the
complex nature of dystroglycanopathies and highlights the potential role of monosaccharides
in future therapeutic approaches. Less

• Keywords: šećer; POMT2; miotube; oksidacijski stres; distroglikan
• Keywords (english): sugar; POMT2; myotubes; oxidative stress; dystroglycan
• Language: croatian
• URN:NBN: urn:nbn:hr:217:745783
• Study programme: Title: Molecular Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra molekularne biologije (sveučilišni/a magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-02-27 14:02:18