Suppression of hepatic hepcidin expression in response to acute iron deprivation is associated with an increase of matriptase-2 protein.
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.
Department of Cell and Developmental Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. zhanga@ohsu.edu
An-Sheng
AS
Zhang
Sheila A
SA
Anderson
Jiaohong
J
Wang
Fan
F
Yang
Kristina
K
DeMaster
Riffat
R
Ahmed
Christopher P
CP
Nizzi
Richard S
RS
Eisenstein
Hidekazu
H
Tsukamoto
Caroline A
CA
Enns
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D064451:Hepcidins; D015151:Immunoblotting; D017403:In Situ Hybridization; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D019485:Bone Morphogenetic Proteins; C578703:Hamp protein, rat; D064451:Hepcidins; D019266:Iron, Dietary; D008565:Membrane Proteins; D012333:RNA, Messenger; D014168:Transferrin; D012697:Serine Endopeptidases; C467801:matriptase 2