Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms.

ABSTRACT: To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly controlled by BMP-Smad signalling pathway, but the physiological role of Smad7 in hepcidin regulation remains elusive. We generated and characterized hepatocyte-specific Smad7 knockout mice (Smad7^Alb/Alb ), which showed decreased serum iron, tissue iron, haemoglobin concentration, up-regulated hepcidin and increased phosphor-Smad1/5/8 levels in both isolated primary hepatocytes and liver tissues. Increased levels of hepcidin lead to reduced expression of intestinal ferroportin and mild iron deficiency anaemia. Interestingly, we found no difference in hepcidin expression or phosphor-Smad1/5/8 levels between iron-challenged Smad7^Alb/Alb and Smad7^flox/flox , suggesting other factors

SUBMITTER: An P 

PROVIDER: S-EPMC5980186 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature