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Runx3 regulates iron metabolism via modulation of BMP signalling

Authors
 Hyun-Yi Kim  ;  Jong-Min Lee  ;  You-Soub Lee  ;  Shujin Li  ;  Seung-Jun Lee  ;  Suk-Chul Bae  ;  Han-Sung Jung 
Citation
 CELL PROLIFERATION, Vol.54(12) : e13138, 2021-12 
Journal Title
CELL PROLIFERATION
ISSN
 0960-7722 
Issue Date
2021-12
MeSH
Animals ; Bone Morphogenetic Protein 6 / genetics ; Bone Morphogenetic Protein 6 / metabolism* ; Core Binding Factor Alpha 3 Subunit / genetics ; Core Binding Factor Alpha 3 Subunit / metabolism* ; Hep G2 Cells ; Hepatocytes / metabolism* ; Humans ; Liver / metabolism* ; Mice ; Mice, Knockout ; Signal Transduction*
Keywords
Bmp pathway ; Bmp6 ; Runx3 ; liver iron metabolism
Abstract
Objectives: Runx3, a member of the Runx family of transcription factors, has been studied as a tumour suppressor and key player of organ development. In a previous study, we reported differentiation failure and excessive angiogenesis in the liver of Runx3 knock-out (KO) mice. Here, we examined a function of the Runx3 in liver, especially in iron metabolism.

Methods: We performed histological and immunohistological analyses of the Runx3 KO mouse liver. RNA-sequencing analyses were performed on primary hepatocytes isolated from Runx3 conditional KO (cKO) mice. The effect of Runx3 knock-down (KD) was also investigated using siRNA-mediated KD in functional human hepatocytes and human hepatocellular carcinoma cells.

Result: We observed an iron-overloaded liver with decreased expression of hepcidin in Runx3 KO mice. Expression of BMP6, a regulator of hepcidin transcription, and activity of the BMP pathway were decreased in the liver tissue of Runx3 KO mice. Transcriptome analysis on primary hepatocytes isolated from Runx3 cKO mice also revealed that iron-induced increase in BMP6 was mediated by Runx3. Similar results were observed in Runx3 knock-down experiments using HepaRG cells and HepG2 cells. Finally, we showed that Runx3 enhanced the activity of the BMP6 promoter by responding to iron stimuli in the hepatocytes.

Conclusion: In conclusion, we suggest that Runx3 plays important roles in iron metabolism of the liver through regulation of BMP signalling.
Files in This Item:
T202105688.pdf Download
DOI
10.1111/cpr.13138
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Lee, Jong Min(이종민) ORCID logo https://orcid.org/0000-0002-9466-7644
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187440
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