Effect of erythropoietin on hepcidin, DMT1 with IRE, and hephaestin gene expression in duodenum of rats.
BACKGROUND
Erythropoietin (Epo) is the central regulator of red blood cell production and can stimulate proliferation and differentiation of erythroid progenitor cells. Now, recombinant human erythropoietin (rHuEpo) is widely used in patients with renal disease, chronic anemia, and iron deficiency of early childhood. It has been reported that the enhanced erythropoiesis associated with erythropoietin therapy increases intestinal iron absorption, but the molecular mechanisms underlying are unknown. Therefore, we have investigated the effect of rHuEpo on duodenal iron transport protein synthesis in rats.


METHODS
Male Sprague-Dawley rats weighing 250 g were randomly divided into two groups: (1) rHuEpo injection group (rHuEpo, 500 IU/day, s.c.), and (2) control group (injection of the same volume of saline). After 3 days injection, blood parameters, serum iron status, and non-heme iron concentrations in the liver and duodenum were examined at the fifth day. The mRNA levels and protein synthesis of duodenal divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), and hephaestin (Hp) were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. Hepatic hepcidin mRNA expression was analyzed by RT-PCR.


RESULTS
rHuEpo injection significantly stimulated erythropoiesis and decreased serum iron status, non-heme iron concentrations in the liver and duodenum. DMT1 (+IRE) and Hp expression in duodenum were increased significantly. However, DMT1 (-IRE) and FPN1 expression had no apparent change. Hepatic hepcidin mRNA expression was decreased dramatically, reaching an almost undetectable level in rHuEpo-treated rats.


CONCLUSIONS
rHuEpo administration improved the duodenal iron absorption by increasing the expression of DMT1 (+IRE) and Hp.
Kong
Wei-Na
WN
Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei Province, PR China.
Chang
Yan-Zhong
YZ
Wang
Shu-Min
SM
Zhai
Xing-Li
XL
Shang
Jian-Xiu
JX
Li
Long-Xia
LX
Duan
Xiang-Lin
XL
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006397:Hematinics / Q000494:pharmacology*; D064451:Hepcidins; D007150:Immunohistochemistry; D007408:Intestinal Absorption / Q000187:drug effects*; D035925:Iron-Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099236:Solute Carrier Family 11, Member 2
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D004921:Erythropoietin; D006397:Hematinics; D064451:Hepcidins; D035925:Iron-Regulatory Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D000099236:Solute Carrier Family 11, Member 2; C578702:HAMP protein, human; C578703:Hamp protein, rat; C492163:Heph, protein, rat