Iron regulation mechanisms of bone morphogenetic protein pathway in tissue and plasma

Pauk, Martina (2014) Iron regulation mechanisms of bone morphogenetic protein pathway in tissue and plasma. Doctoral thesis, Faculty of Science > Department of Biology.

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Bone morphogenetic protein 6 (BMP6) is a key regulator of hepcidin expression, a key iron regulatory hormone. We investigated the effect of iron on Bmp6 expression in tissues and plasma, and why other BMPs could not prevent hemochromatosis in Bmp6 -/- mice. In WT mice, 4 hours following iron challenge liver Bmp6 and Hamp expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that iron increased the circulating BMP6 level. On the contrary, in Bmp6 -/- mice, iron challenge lead to a 24 hours delayed and blunted activation of liver Smad signaling and hepcidin expression, that was accompanied by an increased expression of Bmp2, 4, 5 and 9 in the duodenum and Bmp5 and Bmp7 in the liver. High liver Bmp7 expression potentially contributed to the late hepcidin response, which was further supported by BMP7 therapy resulting in an effective hepcidin expression and normalization of serum iron. However, BMP7 synthesis was not associated with iron metabolism, but the causal hepatic injuries where BMP7 represented a form of defense mechanism to the excessive iron accumulation. Our data indicate that iron activated BMP compensatory mechanisms that were not sufficient for preventing hemochromatosis in Bmp6 -/- mice. However, the effective BMP7 therapy suggested that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis.

Item Type: Thesis (Doctoral thesis)
Keywords: iron, hemochromatosis, hepcidin, bone morphogenetic protein
Supervisor: Vukičević, Slobodan
Date: 2014
Number of Pages: 126
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 19 Jan 2015 12:12
Last Modified: 19 Jan 2015 12:12

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