충북대학교 종양연구소에서 다음과 같이 초청세미나를 개최하오니 많은 참여 부탁드립니다.
- 다 음 -
1. 연 자 : 정 한 성 교수 (연세대학교 치과대학)
2. 일 시 : 2016년 02월 03일 (수) 오후 4시
3. 연 제 : Runx3 regulates iron metabolism via modulation of BMP signaling.
4. 장 소 : 종양연구소 세미나실 104호
5. 발 표 내 용
Runt-related transcription factor (Runx) proteins are essential factors of normal mouse development. Runx3, a member of Runx protein family, has been studied as a tumor suppressor and a key player of organ development. Runx3knock-out (KO) mice undergo abnormal development of several organs such as lung and liver. In previous study, we reported differentiation failure and excessive angiogenesis in the liver of Runx3KO mice. Further investigation on the defective liver tissue of Runx3KO mice led us to the relationship between Runx3 and iron metabolism in liver. Prussian blue staining revealed iron overloaded liver of postnatal day 1 (PN1) Runx3KO mice. Hepcidin, a master regulator of cellular iron absorption, decreased in the liver of Runx3KO mice.Furthermore, Ferroportin1, acellular iron exporterbeing down-regulated by Hapcidin binding-inducedinternalization and degradation,increased in the tissue. Interestingly, similar iron overloaded liver is reported in bone morphogenetic protein 6(Bmp6) KO mice. To reveal the possible engagement of BMP signaling with Runx3 deficiency-induced iron overload in liver, we detected BMP6 expression in the liver tissue. The result showed decrease of BMP6 in the liver of Runx3KO mice. The regulation of BMP6 by Runx3 was confirmed using HepaRG cells, the functional human hepatocytes. Runx3knock-down (KD) resulted in decrease of Hepcidinand BMP6in HepaRGcells. The expression of BMP pathway target genes, Id1, Smad7, Atoh8, also decreased by Runx3KD. Furthermore, Runx3 KD in HepaRG cells resulted in the decrease of nuclear Smad4. In conclusion, we suggest that Runx3 plays important roles in iron metabolism of liver though regulation of BMP signaling.