HFE and ALK3 act in the same signaling pathway

Result code in 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>
Result on the web
<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>

Result language
angličtina
Original language name
HFE and ALK3 act in the same signaling pathway
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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