論文 - 詳細
RRC ID | 58847 |
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著者 | Noguchi T, Ikeda M, Murakami M, Masuzawa M, Imamura T, Hashimoto O, Matsui T, Funaba M. |
タイトル | Regulatory expression of bone morphogenetic protein 6 by 2,2'-dipyridyl. |
ジャーナル | Biochim Biophys Acta Gen Subj |
Abstract |
BACKGROUND:Expression of hepcidin, a hormone produced by hepatocytes which negatively regulates the circulating iron levels, is known to be positively regulated by BMP6, a member of transforming growth factor (TGF)-β family. Previous studies have shown that iron status is sensed by sinusoidal endothelial cells of hepatic lamina, leading to the modulation of BMP6 expression. METHODS:ISOS-1, HUVEC, F-2, and SK-HEP1 endothelial cells were treated with either iron or 2,2'-dipyridyl (2DP), a cell-permeable iron-chelator, and expression level of Bmp6 was examined. To identify factors affecting Bmp6 transcription, stimulus screening for regulator of transcription (SSRT) was developed. RESULTS:Treatment with iron slightly increased the expression levels of Bmp6, while 2DP unexpectedly increased Bmp6 expression in a dose-dependent manner. 2DP-induced Bmp6 expression was resistant to co-treatment with iron. 2DP-induced Bmp6 expression was also detected in HUVEC, F-2 cells, and SK-HEP1 cells. Luciferase-based reporter assays indicated that forced expression of JunB increased the transcription of Bmp6. 2DP induced phosphorylation of JunB; co-treatment with SP600125 blocked the 2DP-induced Bmp6 expression partially. JunB-induced Bmp6 transcription was not affected by mutations of putative JunB-responsive elements. Some endoplasmic reticulum stress inducers increased the expression of Bmp6. SSRT revealed pathways regulating Bmp6 transcription positively and negatively. Hepa1-6 liver cells and C2C12 myogenic cells were prone to 2DP induced Bmp6 expression. CONCLUSIONS:The present study reveals non‑iron-regulated Bmp6 expression in endothelial cells. GENERAL SIGNIFICANCE:Regulatory expression of Bmp6 may be important as a key step for fine tuning of BMP activity. |
巻・号 | 1864(8) |
ページ | 129610 |
公開日 | 2020-8-1 |
DOI | 10.1016/j.bbagen.2020.129610 |
PII | S0304-4165(20)30122-7 |
PMID | 32251709 |
MeSH | 2,2'-Dipyridyl / pharmacology* Animals Bone Morphogenetic Protein 6 / genetics* Cells, Cultured Dose-Response Relationship, Drug Gene Expression Profiling Gene Expression Regulation / drug effects* Humans Iron / pharmacology Mice |
IF | 3.681 |
引用数 | 0 |
リソース情報 | |
ヒト・動物細胞 | Hepa 1-6(RCB1638) |