Autokrine Regulation von Hepcidin in der Leber
Dissertation
Autoren
Fritz, Sarah
Fakultäten
Medizinische FakultätZusammenfassung
BACKGROUNDS AND AIMS:
Hepcidin is an antimicrobial peptide and the central regulator of iron metabolism. Hepcidin is evidentially upregulated by iron overload as well as inflammation and downregulated by hypoxia or iron deficiency. However, the
underlying mechanisms of hepcidin regulation are not completely understood yet. This study analyzed an autocrine regulation of hepcidin in human liver cells.
METHODS:
Human liver cells (HepG2, Hep3B) were stimulated with synthetic hepcidin. The expression of endogenous hepcidin was studied by quantitative RT-PCR, western blot, and immunofluorescence.
RESULTS:
In human liver cell lines, hepcidin showed an autocrinally downregulated expression after stimulation with synthetic hepcidin that was not seen in non-hepatic cell lines and is thereby thought to be liver-specific. Analyzing the established hepcidin regulatory pathways revealed that those do not participate in the autocrine suppression of hepcidin. Interestingly, results of the present study point to a role for the hepcidin receptor ferroportin in that process. Expression of ferroportin was markedly reduced in human liver cell lines after treatment with hepcidin. Moreover, cells treated with a specific ferroportin siRNA showed downregulated hepcidin expression and were not able to further decrease hepcidin mRNA synthesis after addition of exogenous hepcidin.
CONCLUSIONS:
Hepcidin is autocrinally regulated and this regulation most likely is a liver-specific effect. The observed reduction in ferroportin expression in the presence of synthetic hepcidin is probably part of a new, hitherto unknown signaling pathway of the autocrine downregulation.
Erstellung / Fertigstellung
2011
Normierte Schlagwörter
Eisenstoffwechsel [GND]Genregulation [GND]
Antimicrobial cationic peptides [MeSH]
Hepcidins [MeSH]
Liver. Metabolism [MeSH]
Schlagwörter
EisenregulationDDC-Sachgruppe
DDC 610 / Medicine & healthMetadata
Zur LanganzeigeZitiervorlage
Fritz, Sarah (2012): Autokrine Regulation von Hepcidin in der Leber. Open Access Repositorium der Universität Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-2678