title: B-cell translocation gene 2 promotes hepatic hepcidin production via induction of Yin Yang 1.
abstract: Hepcidin is a peptide hormone secreted in the liver and plays a key role in maintaining iron homeostasis. Here, we demonstrate that B-cell translocation gene 2 (BTG2) is a key player in hepatic hepcidin regulation via induction of Yin Yang 1 (YY1). Hepatic hepcidin gene expression significantly enhanced by fasting states and glucagon exposure led to induction of gluconeogenic gene expression, and elevated serum hepcidin production in mice. Notably, overexpression of BTG2 using adenoviral system (Ad-BTG2) significantly elevated serum hepcidin levels via a significant induction of YY1 gene transcription. Immunoprecipitation studies demonstrated that BTG2 physically interacted with YY1 and recruited on the hepcidin gene promoter. Finally, ablation of hepatic BTG2 gene by gene silencing markedly attenuated the elevation of serum hepcidin production along with YY1 and hepcidin mRNA expression in fasting state. Likewise, forskolin (FSK)-stimulated hepcidin promoter activity was dramatically disrupted by endogenous BTG2 knockdown. Overall, our current study provides a novel molecular mechanism of BTG2-mediated induction of hepcidin gene expression, thereby contributing to a better understanding of the hepatic hepcidin production involved in iron homeostasis.
authors.affiliation: School of Applied Biosciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Seung-Lark
authors.initials: SL
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, School of Engineering, Daegu University, Gyeongbuk 712-714, Republic of Korea.
authors.forename: Won-Gu
authors.initials: WG
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: hwchang@yu.ac.kr.
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
authors.affiliation: School of Applied Biosciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: ydkim94@gamil.com.
authors.forename: Yong Deuk
authors.initials: YD
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D017931:DNA Primers; D005943:Gluconeogenesis; D064451:Hepcidins / Q000096:biosynthesis* / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D050986:YY1 Transcription Factor / Q000096:biosynthesis*
chemical_list: C489435:Btg2 protein, mouse; D017931:DNA Primers; D064451:Hepcidins; D017874:Immediate-Early Proteins; D025521:Tumor Suppressor Proteins; D050986:YY1 Transcription Factor
keywords: B-translocation gene 2 (BTG2); Gene expression; Hepcidin; Yin Yang 1