Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice.

ABSTRACT: A failure of iron to appropriately regulate liver hepcidin production is central to the pathogenesis of hereditary hemochromatosis. SMAD1/5 transcription factors, activated by bone morphogenetic protein (BMP) signaling, are major regulators of hepcidin production in response to iron; however, the role of SMAD8 and the contribution of SMADs to hepcidin production by other systemic cues remain uncertain. Here, we generated hepatocyte Smad8 single (Smad8^fl/fl ;Alb-Cre⁺ ), Smad1/5/8 triple (Smad158;Alb-Cre⁺ ), and littermate Smad1/5 double (Smad15;Alb-Cre⁺ ) knockout mice to investigate the role of SMAD8 in hepcidin and iron homeostasis regulation and liver injury. We found that Smad8;Alb-Cre⁺ mice exhibited no iron phenotype, whereas Smad

SUBMITTER: Wang CY 

PROVIDER: S-EPMC6874904 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature