HFE and ALK3 act in the same signaling pathway
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10419615" target="_blank" >RIV/00216208:11110/20:10419615 - isvavai.cz</a>
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1qqM0chdbG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1qqM0chdbG</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.023" target="_blank" >10.1016/j.freeradbiomed.2020.08.023</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
HFE and ALK3 act in the same signaling pathway
Popis výsledku v původním jazyce
Hepcidin deficiency leads to iron overload by increased dietary iron uptake and iron release from storage cells. The most frequent mutation in Hfe leads to reduced hepcidin expression and thereby causes iron overload. Recent findings suggested that HFE activates hepcidin expression predominantly via the BMP type I receptor ALK3. Here, we investigated whether HFE exclusively utilizes ALK3 or other signaling mechanisms also. We generated mice with double deficiency of Hfe and hepatocyte-specific Alk3 and compared the iron overload phenotypes of these double knockout mice to single hepatocyte-specific Alk3 deficient or Hfe knockout mice. Double Hfe(-/-)/hepatic Alk3(fl/fl);Alb-Cre knockouts develop a similar iron overload phenotype compared to single hepatocyte-specific Alk3 deficient mice hallmarked by serum iron levels, tissue iron content and hepcidin levels of similar grades. HFE protein levels were increased in Alk3(fl/fl);Alb-Cre mice compared to Alk3(fl/fl) mice, which was caused by iron overload - and not by Alk3 deficiency. The data provide evidence by genetic means that 1. HFE exclusively uses the BMP type I receptor ALK3 to induce hepcidin expression and 2. HFE protein expression is induced by iron overload, which further emphasizes the iron sensing function of HFE.
Název v anglickém jazyce
HFE and ALK3 act in the same signaling pathway
Popis výsledku anglicky
Hepcidin deficiency leads to iron overload by increased dietary iron uptake and iron release from storage cells. The most frequent mutation in Hfe leads to reduced hepcidin expression and thereby causes iron overload. Recent findings suggested that HFE activates hepcidin expression predominantly via the BMP type I receptor ALK3. Here, we investigated whether HFE exclusively utilizes ALK3 or other signaling mechanisms also. We generated mice with double deficiency of Hfe and hepatocyte-specific Alk3 and compared the iron overload phenotypes of these double knockout mice to single hepatocyte-specific Alk3 deficient or Hfe knockout mice. Double Hfe(-/-)/hepatic Alk3(fl/fl);Alb-Cre knockouts develop a similar iron overload phenotype compared to single hepatocyte-specific Alk3 deficient mice hallmarked by serum iron levels, tissue iron content and hepcidin levels of similar grades. HFE protein levels were increased in Alk3(fl/fl);Alb-Cre mice compared to Alk3(fl/fl) mice, which was caused by iron overload - and not by Alk3 deficiency. The data provide evidence by genetic means that 1. HFE exclusively uses the BMP type I receptor ALK3 to induce hepcidin expression and 2. HFE protein expression is induced by iron overload, which further emphasizes the iron sensing function of HFE.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30105 - Physiology (including cytology)
Návaznosti výsledku
Projekt
—
Návaznosti
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Free Radical Biology & Medicine
ISSN
0891-5849
e-ISSN
—
Svazek periodika
160
Číslo periodika v rámci svazku
November
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
5
Strana od-do
501-505
Kód UT WoS článku
000595450000007
EID výsledku v databázi Scopus
2-s2.0-85090367343