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B-cell translocation gene 2 enhances fibroblast growth factor 21 production by inducing Kruppel-like factor 15
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
- Publication Year :
- 2018
-
Abstract
- Fibroblast growth factor 21 (FGF21) is a hormone that is vital for the regulation of metabolic homeostasis. In the present study, we report that Kruppel-like factor 15 (KLF15) is a novel mediator of b-cell translocation gene 2 (BTG2)-induced FGF21 biosynthesis. The expression levels of hepatic Fgf21, Btg2, and Klf15, and the production of serum FGF21 increased significantly in fasted and forskolin (FSK)-treated mice. The overexpression of Btg2 using an adenoviral delivery system elevated FGF21 production by upregulating Klf15 transcription. Interaction studies indicated that BTG2 was co-immunoprecipitated with KLF15 and recruited by the Fgf21 promoter. The disruption of hepatic Btg2 and Klf15 genes markedly attenuated the induction of Fgf21 expression and FGF21 biosynthesis in fasted mice. Similarly, the FSK-mediated induction of Fgf21 promoter activity was strikingly ablated by silencing of Btg2 and Klf15. Taken together, these findings suggest that KLF15 and BTG2 are mediators of fasting-induced hepatic FGF21 expression. Therefore, targeting BTG2 and KLF15 might be a therapeutically important strategy for combat metabolic dysfunction.
- Subjects :
- 0301 basic medicine
Male
FGF21
Transcription, Genetic
Kruppel-Like Transcription Factors
lcsh:Medicine
Chromosomal translocation
KLF15
Article
Cell Line
Immediate-Early Proteins
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Mediator
Transcription (biology)
Gene silencing
Animals
lcsh:Science
Promoter Regions, Genetic
Author Correction
Multidisciplinary
BTG2
Forskolin
Tumor Suppressor Proteins
lcsh:R
Colforsin
Fasting
Cell biology
Up-Regulation
Fibroblast Growth Factors
030104 developmental biology
chemistry
Liver
Hepatocytes
lcsh:Q
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....2ab3d7a3ca231e87906defb0a3c65ffd