Effects of TMPRSS6 on the Iron Metabolism of Rats in the Prevention of Exercise-Associated Anemia by Hypoxia

Objective:To illuminate effects of hypoxia on iron metabolism in the prevention of exercise-associated anemia.Methods:24 male Wistar rats were randomly divided into three groups,the control group(CG),and the strenuously exercised group(EG),and the hypoxia exercise group(13.6% O2,8h/d,HE).The content of erythropoietin(EPO) and serum Ferritin(SF) were examined by ELISA kits(Abcam).The mRNAs of hepatic hepcidin,hypoxia-inducible factor 1(HIF-1),transmembrane serine proteases 6(TMPRSS6) and hemojuvelin(m-HJV) were examined by RT-PCR.Results:1)Compared with EG,the Hb,SF,and iron storage in bone marrow of HE were significantly increased(Hb:HE:139.56±10.24 g/L,EG:113.16±17.36 g/L,P<0.01;SF:HE:29.72±2.85 ng/mL,EG:18.23±3.57 ng/mL,P<0.01;iron storage in bone marrow:HE:75.98±7.08 μg/g,EG:62.19±8.98 μg/g,P<0.05).2)Compared with EG,the mRNAs of HIF-1and TMPRSS6 in the liver of HE were significantly increased.3)The mRNAs of HJV and Hepcidin of HE were decreased compared to EG,and the iron storage in liver was decreased in HE(HE:80.18±13.66 μg/g,EG:111.51±12.64 μg/g,P<0.01).Conclusions:Moderate hypoxia plays an important role in preventing exercise-induced iron deficiency.Exposure to hypoxia,the increased HIF-1 in liver stimulates the expression of TMPRSS6,and as a result,the synthesis of Hepcidin is decreased,which leads to the iron mobilization in liver to meet the requirement of iron during strenuous exercise,which prevents the exercise-associated anemia.