Zhang, An-Sheng and Anderson, Sheila A. and Wang, Jiaohong and Yang, Fan and DeMaster, Kristina and Ahmed, Riffat and Nizzi, Christopher P. and Eisenstein, Richard S. and Tsukamoto, Hidekazu and Enns, Caroline A. (2011) Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein. Blood, 117 (5). pp. 1687-1699. ISSN 0006-4971 http://resolver.caltech.edu/CaltechAUTHORS:20110302-114003661
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Recent studies demonstrate a pivotal role for bone morphogenic protein-6 (BMP6) and matriptase-2, a protein encoded by the TMPRSS6 gene, in the induction and suppression of hepatic hepcidin expression, respectively. We examined their expression profiles in the liver and showed a predominant localization of BMP6 mRNA in nonparenchymal cells and exclusive expression of TMPRSS6 mRNA in hepatocytes. In rats fed an iron-deficient (ID) diet for 24 hours, the rapid decrease of transferrin saturation from 71% to 24% (control vs ID diet) was associated with a 100-fold decrease in hepcidin mRNA compared with the corresponding controls. These results indicated a close correlation of low transferrin saturation with decreased hepcidin mRNA. The lower phosphorylated Smad1/5/8 detected in the ID rat livers suggests that the suppressed hepcidin expression results from the inhibition of BMP signaling. Quantitative real-time reverse transcription polymerase chain reaction analysis revealed no significant change in either BMP6 or TMPRSS6 mRNA in the liver. However, an increase in matriptase-2 protein in the liver from ID rats was detected, suggesting that suppression of hepcidin expression in response to acute iron deprivation is mediated by an increase in matriptase-2 protein levels.
|Additional Information:||© 2011 American Society of Hematology. Submitted June 4, 2010; accepted November 17, 2010. Prepublished online as Blood First Edition paper, November 29, 2010. We thank Dr Thomas Bartnikas and Dr Mark Fleming at Harvard University for Tmprss6^(-/-) mice liver tissues and Julia Maxson, Maja Chloupkova, and Junwei Gao for critical reading of this manuscript and helpful comments. This work was supported by NIH DK080765 (A.-S.Z.), NIH DK066600 (R.S.E.), NIH P50AA11199 (H.T.), NIH R24AA12885 (H.T.), and NIH DK72166 (C.A.E.). Author Contribution: A.-S.Z. designed the research, performed experiments, and wrote the paper. S.A.A. and R.S.E. designed the research and performed experiments; J.W., F.Y., K.D., R.A., C.P.N., and H.T. performed experiments; and C.A.E. designed the research and edited the paper. The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.|
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|Deposited By:||Jason Perez|
|Deposited On:||03 Mar 2011 16:09|
|Last Modified:||03 Mar 2011 16:09|
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