NDLI: HNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells

Content Provider	Springer Nature Link
Author	Shi, Wencai Wang, Heyang Zheng, Xuan Jiang, Xin Xu, Zheng Shen, Hui Li, Min
Copyright Year	2016
Abstract	Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4α (HNF-4α) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4α on hepcidin expression was observed by transfecting specific HNF-4α small interfering RNA (siRNA) or plasmids into HepG2 cells. Both direct and indirect mechanisms involved in the regulation of HNF-4α on hepcidin were detected by real-time PCR, Western blotting, chromatin immunoprecipitation (chIP), and reporter genes. It was found that HNF-4α suppressed hepcidin messenger RNA (mRNA) and protein expressions in HepG2 cells, and this suppressive effect was independent of the potential HNF-4α response elements. Phosphorylation of SMAD1 but not STAT3 was inactivated by HNF-4α, and the SMAD4 response element was found essential to HNF-4α-induced hepcidin reduction. Neither inhibitory SMADs, SMAD6, and SMAD7 nor BMPR ligands, BMP2, BMP4, BMP6, and BMP7 were regulated by HNF-4α in HepG2 cells. BMPR1A, but not BMPR1B, BMPR2, ActR2A, ActR2B, or HJV, was decreased by HNF-4α, and HNF4α-knockdown-induced stimulation of hepcidin could be entirely blocked when BMPR1A was interfered with at the same time. In conclusion, the present study suggests that HNF-4α has a suppressive effect on hepcidin expression by inactivating the BMP pathway, specifically via BMPR1A, in HepG2 cells.
Starting Page	294
Ending Page	304
Page Count	11
File Format	PDF
ISSN	01634984
Journal	Biological Trace Element Research
Volume Number	176
Issue Number	2
e-ISSN	15590720
Language	English
Publisher	Springer US
Publisher Date	2016-09-23
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	HNF-4α·hepcidin pSMAD1/5/8 BMPR1A Biochemistry Biotechnology Nutrition Oncology
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Inorganic Chemistry

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