Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein

An-Sheng Zhang, Sheila A. Anderson, Jiaohong Wang, Fan Yang, Kristina DeMaster, Riffat Ahmed, Christopher P. Nizzi, Richard S. Eisenstein, Hidekazu Tsukamoto, Caroline Enns

Research output: Contribution to journalArticle

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Abstract

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 BMP6mRNA in nonparenchymal cells and exclusive expression of TMPRSS6 mRNAin 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 realtime 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.

Original languageEnglish (US)
Pages (from-to)1687-1899
Number of pages213
JournalBlood
Volume117
Issue number5
DOIs
StatePublished - Feb 3 2011

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Hepcidins
Iron
Liver
Rats
Transferrin
Nutrition
Proteins
Messenger RNA
Bone
Diet
Bone and Bones
Polymerase chain reaction
Transcription
Reverse Transcription
Hepatocytes
Genes
matriptase 2
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein. / Zhang, An-Sheng; Anderson, Sheila A.; Wang, Jiaohong; Yang, Fan; DeMaster, Kristina; Ahmed, Riffat; Nizzi, Christopher P.; Eisenstein, Richard S.; Tsukamoto, Hidekazu; Enns, Caroline.

In: Blood, Vol. 117, No. 5, 03.02.2011, p. 1687-1899.

Research output: Contribution to journalArticle

Zhang, A-S, Anderson, SA, Wang, J, Yang, F, DeMaster, K, Ahmed, R, Nizzi, CP, Eisenstein, RS, Tsukamoto, H & Enns, C 2011, 'Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein', Blood, vol. 117, no. 5, pp. 1687-1899. https://doi.org/10.1182/blood-2010-06-287292
Zhang, An-Sheng ; Anderson, Sheila A. ; Wang, Jiaohong ; Yang, Fan ; DeMaster, Kristina ; Ahmed, Riffat ; Nizzi, Christopher P. ; Eisenstein, Richard S. ; Tsukamoto, Hidekazu ; Enns, Caroline. / Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein. In: Blood. 2011 ; Vol. 117, No. 5. pp. 1687-1899.
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