Povezanost serumske koncentracije željeza s ekspresijom BMP6 molekula u jetri - moguća uloga u hemokromatozi

master's thesis

• Title (english): Correlation between serum iron levels and expression of BMP6 molecules in liver - the possible role in hemochromatosis
• Author: Tomo Svaguša
• Mentor: Slobodan Vukičević (mentor)
• Committee member: Lovorka Grgurević (predsjednik povjerenstva)
• Committee member: Zdravko Petanjek (član povjerenstva)
• Committee member: Slobodan Vukičević (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Anatomy and Clinical Anatomy); Zagreb
• Defense date and country: 2014-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy

Abstract

Smatra se da ključnu fiziološku ulogu u regulaciji homeostaze željeza ima cirkulirajući peptidni hormon hepcidin. Njegova ekspresija u stanicama jetre in vivo potaknuta je unutarstaničnim signalnim putem molekule BMP6. Pri induciranom opterećenju organizma željezom, u jetri WT miševa zabilježen je značajan porast ekspresije Bmp6 gena, što je u korelaciji s porastom ekspresije hepcidina u jetri. Histološka građa jetre WT miševa je očuvana. Suprotno tome, u pokusima s miševima s izbačenim genom za BMP6 (Bmp6 KO), pri induciranom opterećenju željezom nalazimo masivno nakupljanje željeza u tkivu te morfološke promjene jetre koje odgovaraju hemokromatozi. Rezultati govore u prilog tezi o središnjoj ulozi BMP6 i hepcidina u homeostazi željeza. Jetra ima središnju ulogu u sintezi BMP6. S obzirom na to da su poremećaji metabolizma željeza od velikog kliničkog značaja, daljnja istraživanja trebala bi biti usmjerena na razvoj biomarkara za dijagnostiku i praćenje tijeka bolesti.

Abstract (english)

A circulating peptide hormone hepcidin is considerred as a key-regulator of the iron homeostasis. In the liver cells, its expression in vivo is induced by a BMP6 intracellular signaling pathway. In the liver of WT mice fed an iron-supplemented diet, we detected a significant increase in the expression of Bmp6 gene which also correlated with the liver expression of hepcidin. A histological structure of the liver tissue was unharmed. On the other hand, in the liver of Bmp6 KO mice fed an iron-supplemented diet we detected a massive iron overload in the liver tissue and the morphological characteristics of hemochromatosis. The results confirmed a hypothesis of the central role of BMP6 and hepcidin in the regulation of the iron homeostasis. Also, we concluded that the synthesis of BMP6 takes place mainly in the liver. As the iron metabolic disorders are rather frecquent and clinically important, further reasearches should be focused on the possible development of biomarkers for the diagnosis and monitoring of the diseases.

• Keywords: BMP6; hepcidin; željezo; hemokromatoza; jetra
• Keywords (english): BMP6; hepcidin; iron; hemochromatosis; liver
• Language: croatian
• URN:NBN: urn:nbn:hr:105:143976
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2015-10-02 11:35:22