Deficiency of the BMP Type I receptor ALK3 partly protects mice from anemia of inflammation

BMC Physiology
Inka GallitzAndrea U Steinbicker

Abstract

Inflammatory stimuli induce the hepatic iron regulatory hormone hepcidin, which contributes to anaemia of inflammation (AI). Hepcidin expression is regulated by the bone morphogenetic protein (BMP) and the interleukin-6 (IL-6) signalling pathways. Prior results indicate that the BMP type I receptor ALK3 is mainly involved in the acute inflammatory hepcidin induction four and 72 h after IL-6 administration. In this study, the role of ALK3 in a chronic model of inflammation was investigated. The intact, heat-killed bacterium Brucella abortus (BA) was used to analyse its effect on the development of inflammation and hypoferremia in mice with hepatocyte-specific Alk3-deficiency (Alk3fl/fl; Alb-Cre) compared to control (Alk3fl/fl) mice. An iron restricted diet prevented development of the iron overload phenotype in mice with hepatocyte-specific Alk3 deficiency. Regular diet leads to iron overload and increased haemoglobin levels in these mice, which protects from the development of AI per se. Fourteen days after BA injection Alk3fl/fl; Alb-Cre mice presented milder anaemia (Hb 16.7 g/dl to 11.6 g/dl) compared to Alk3fl/fl control mice (Hb 14.9 g/dl to 8.6 g/dl). BA injection led to an intact inflammatory response in all groups of mi...Continue Reading

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Citations

Feb 9, 2019·Experimental Biology and Medicine·David H Wu, Antonis K Hatzopoulos
Sep 27, 2019·Nature Reviews. Nephrology·Rachel P L van SwelmDorine W Swinkels
Dec 27, 2019·Current Opinion in Anaesthesiology·Thomas B BartnikasCaroline A Enns

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Methods Mentioned

BETA
flow cytometry
electrophoresis

Software Mentioned

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