The role of Bone Morphogenetic Proteins in the liver

BMPs (Bone Morphogenetic Proteins) are known as modulators of iron homeostasis in the liver. BMPs are induced due to an elevated iron uptake. Via BMP receptors and the BMP-coreceptor HJV (Hämojuvelin), the hepcidin expression increases to limit the intestinale iron uptake. Our analysis revealed BMP6 as the main regulator of hepcidin. Additionally, we could show that BMP6 is expressed in the small intestine according to the iron level and is transported via the bloodstream to the liver to regulate the expression of hepcidin (Arndt et al., 2010 Gastroenterology).


 

Fig. 1: Regulation of iron homeostasis

Furthermore, BMPs play a major role in many cancer diseases. In our studies we could show that activation of the BMP specific smad signaling cascade is involved in progression of hepatocellular carcinoma (HCC) (Maegdefrau et al., 2012 Exp Mol Pathol).

Fig. 2: Pathogenesis of the HCC (hepatocellular carcinoma)


In current studies we investigate the function of BMPs in NAFLD (non-alcoholic fatty liver disease), because research on NASH (non-alcoholic steatohepatitis) mouse models and NAFLD patients showed an increased BMP6 expression in the damaged liver.

 

Fig. 3: BMP6 mRNA expression in liver tissue of mice after feeding NASH-inducing diets (left: HF (high fat) diet; right: MCD (methionine-choline deficient) diet)

Fig. 4: BMP6 immunohistochemical staining of liver tissue of an NAFLD patient compared to normal liver tissue (ctr.)

Research focus: Melanoma

Other research focuses