Your browser doesn't support javascript.
loading
Activin B Induces Noncanonical SMAD1/5/8 Signaling via BMP Type I Receptors in Hepatocytes: Evidence for a Role in Hepcidin Induction by Inflammation in Male Mice.
Canali, Susanna; Core, Amanda B; Zumbrennen-Bullough, Kimberly B; Merkulova, Maria; Wang, Chia-Yu; Schneyer, Alan L; Pietrangelo, Antonello; Babitt, Jodie L.
Afiliación
  • Canali S; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
  • Core AB; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
  • Zumbrennen-Bullough KB; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
  • Merkulova M; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
  • Wang CY; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
  • Schneyer AL; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
  • Pietrangelo A; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
  • Babitt JL; Program in Anemia Signaling Research (S.C., A.B.C., K.B.Z.-B., M.M., C.-Y.W., J.L.B.), Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Center for Hemochromatosis (S.C., A.P.), Univer
Endocrinology ; 157(3): 1146-62, 2016 Mar.
Article en En | MEDLINE | ID: mdl-26735394
Induction of the iron regulatory hormone hepcidin contributes to the anemia of inflammation. Bone morphogenetic protein 6 (BMP6) signaling is a central regulator of hepcidin expression in the liver. Recently, the TGF-ß/BMP superfamily member activin B was implicated in hepcidin induction by inflammation via noncanonical SMAD1/5/8 signaling, but its mechanism of action and functional significance in vivo remain uncertain. Here, we show that low concentrations of activin B, but not activin A, stimulate prolonged SMAD1/5/8 signaling and hepcidin expression in liver cells to a similar degree as canonical SMAD2/3 signaling, and with similar or modestly reduced potency compared with BMP6. Activin B stimulates hepcidin via classical activin type II receptors ACVR2A and ACVR2B, noncanonical BMP type I receptors activin receptor-like kinase 2 and activin receptor-like kinase 3, and SMAD5. The coreceptor hemojuvelin binds to activin B and facilitates activin B-SMAD1/5/8 signaling. Activin B-SMAD1/5/8 signaling has some selectivity for hepatocyte-derived cells and is not enabled by hemojuvelin in other cell types. Liver activin B mRNA expression is up-regulated in multiple mouse models of inflammation associated with increased hepcidin and hypoferremia, including lipopolysaccharide, turpentine, and heat-killed Brucella abortus models. Finally, the activin inhibitor follistatin-315 blunts hepcidin induction by lipopolysaccharide or B. abortus in mice. Our data elucidate a novel mechanism for noncanonical SMAD activation and support a likely functional role for activin B in hepcidin stimulation during inflammation in vivo.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatocitos / Activinas / Receptores de Proteínas Morfogenéticas Óseas de Tipo 1 / Hepcidinas / Inflamación Límite: Animals / Humans / Male Idioma: En Revista: Endocrinology Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatocitos / Activinas / Receptores de Proteínas Morfogenéticas Óseas de Tipo 1 / Hepcidinas / Inflamación Límite: Animals / Humans / Male Idioma: En Revista: Endocrinology Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos