Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Effects of Hepcidin Hormone on the Gene Expression of Ferroportin and Divalent Metal Transporter 1 in Caco-2 Cells and J774 Cells

Caco-2 소장세포와 J774 대식세포에서 Hepcidin 호르몬이 철분 수송체 Ferroportin과 Divalent Metal Transporter 1의 유전자 발현에 미치는 영향

  • 채선주 (경희대학교 생활과학대학 식품영양학과) ;
  • 정자용 (경희대학교 생활과학대학 식품영양학과)
  • Published : 2008.06.30
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Abstract

Hepcidin is a peptide hormone produced by the liver, of which secretion is closely related to iron status in the body. However, little is known about the molecular mechanism(s) by which this peptide regulates body iron homeostasis. The purpose of this study was to determine the effects of hepcidin treatment within the physiological concentration range on the expressions of two different iron transporter proteins-ferroportin (FPN) and divalent metal transporter 1 (DMT1). Differentiated Caco-2 intestinal cells and macrophage J774 cells were treated with either synthetic hepcidin or hepcidin-rich fraction separated from human urine at the concentration of 10 nM and 100 nM for 24 hours. Results show that hepcidin treatment in differentiated Caco-2 cells or in J774 cells did not change the level of either FPN mRNA or DMT1 mRNA. On the other hand, hepcidin treatment at the dose of 100 nM significantly decreased the FPN protein levels and DMT1 protein levels in differentiated Caco-2 cells. Similarly, urinary hepcidin treatment (10 nM & 100 nM) also significantly decreased the levels of FPN and DMT1 proteins in J774 macrophage cells. These results showed that hepcidin might play an important role in the regulation of iron homeostasis by lowering the protein levels of iron transporter FPN and DMT1 both in enterocytes and in macrophage cells.

본 연구에서는 소장세포(Caco-2)와 대식세포(J774)를 이용하여 FPN과 DMT1의 유전자 발현에 hepcidin 펩타이드 호르몬이 미치는 영향을 알아보기 위하여 수행되었으며 그 결과를 요약하면 다음과 같다. Caco-2 세포에서 FPN과 DMT1의 mRNA 및 단백질 수준은 분화 진행에 따라 비례하여 증가하였으며, 특히 DMT1 단백질은 분화 초기에는 거의 발현되지 않다가 분화 7일째에 비로소 발현되기 시작한 후 급격히 증가하여 분화 17일째에는 7일째에 비해 단백질 수준이 10배 이상 크게 증가되었다. 분화된 Caco-2 세포에서 소변 hepcidin과 합성 hepcidin을 100 nM 농도로 24시간 동안 처리하였을 때, FPN 단백질 수준이 대조군에 비해 각각 60%와 70% 수준으로 유의하게 감소하였다. DMT1 단백질의 경우, 소변 hepcidin 100 nM 농도에서만 대조군의 55% 수준으로 유의하게 감소되었다. J774 세포에 소변 hepcidin 혹은 합성 hepcidin을 24시간 처리한 결과, 10 nM과 100 nM 농도에서 모두 대조군에 비해 FPN 단백질 수준이 유의적으로 감소하는 것으로 나타났으며, DMT1 단백질 수준도 소변 hepcidin 10 nM과 100 nM 처리에 의해 각각 대조군의 40%와 37% 수준으로 유의하게 감소하였다. 분화된 Caco-2 세포와 J774 세포에서 10 nM 혹은 100 nM 농도의 hepcidin 처리 시 DMT1 mRNA와 FPN mRNA 수준에는 영향을 미치지 않는 것으로 나타났으며, 이로 볼 때 hepcidin은 전사과정의 조절보다는 DMT1과 FPN 단백질로의 번역과정을 억제하거나 분해 속도를 촉진함으로써 이들 단백질의 수준을 낮추는 것으로 보인다. 이상의 결과는, hepcidin 펩타이드 호르몬이 DMT1 단백질과 FPN 단백질의 수준을 억제함으로써 체내 철분 대사 조절에 중요하게 관여함을 나타낸다. 특히 소장세포와 대식세포에 동시에 작용함으로써, 소장에서의 철분 흡수와 대식세포에서의 철분 방출을 효율적으로 억제하는 조절 인자로 작용할 수 있음을 제시한다. 앞으로 hepcidin의 생성 및 분비를 조절하는 요인에 대한 연구와 hepcidin이 실제 세포 내외로의 철분의 수송이 미치는 영향에 대한 기능적 연구가 계속적으로 이루어져야 할 것으로 사료된다.

Keywords

References

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