Z Gastroenterol 2014; 52 - P_3_05
DOI: 10.1055/s-0033-1360924

Changes of gene expression of different BMP-proteins in liver in different mouse and rat models of acute phase reaction

S Ahmad 1, V Giannelli 2, N Naz 1, I Malik 1, A Amanzada 1, G Ramadori 1, F Moriconi 1
  • 1Universitätsmedizin Göttingen, Klinik für Gastroenterologie und Endokrinologie, Goettingen, Germany
  • 2University „La Sapienza“, Department of Gastroenterology, Rome, Italy

Background and Aim: Hepcidin has been considered to have a pivotal role in regulating hepatic iron metabolism. Recently proteins of the TGF-family, manly BMP-4, BMP-6 and BMP-9 have been attributed an additional role in iron metabolism control.

As hepcidin is a positive acute phase protein, we aimed to study changes of gene expression of BMPs in two murine models of acute phase reaction (APR), to individuate the main cellular source of BMP-6 in the liver and to determine the role of IL-6 on BMPs gene expression using mice knock out for IL-6.

Methods: Wild type and IL-6 ko-mice were treated either with turpentine oil (TO) intramuscularly or with lipopolysaccharide (LPS) intraperitoneally. Control animals were anesthetized but were not given any injection to avoid any kind of trauma and tissue damage. Animals were also injected with IL-6, TNF-α or IL-1β intraperitoneally. Animals were sacrificed at different time points up to 24h after treatment and livers were taken snap-frozen in liquid nitrogen and stored at -80 °C.

Gene expression was analyzed using Real-Time PCR analysis of total RNA using primers specific for BMP-4, 6- and 9. Cryostat liver sections were used for immunostaining using a specific antibody against BMP-6. Liver proteins were analysed by western blot.

Results: A significant up-regulation of gene-expression of the three BMPs (2.5- to 11-folds) after the onset of APR (p<.001) in both models was found. Up-regulation of BMP-6-gene-expression was found starting at 2 hour (2.06-folds) after APR induction with a peak of 3.1-fold at 6h.

In mice treated with TO/LPS, the IL-6 wild-type animals showed a higher up regulation of BMPs than the IL-6 knock out series. BMP-6 changing in gene expression after 6h was respectively 5.2 folds vs. 0.58 in wild-type vs. knock out. The behaviour of hepatic hepcidin-gene-expression was similar to that of the BMP-genes.

Conclusions: BMPs are positive acute-phase proteins and behave under different acute phase conditions in a manner similar to that of hepcidin. IL-6 is a potent inducer of all these proteins but is dispensable under the acute phase conditions studied.