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Type 10 17β-hydroxysteroid dehydrogenase expression is regulated by C/EBPβ in HepG2 cells
Mirja Rotinen1, Joaquín Villar, Jon Celay
1Department of Health Sciences, Universidad Pública de Navarra, Avda Barañain, 31008 Pamplona, Spain.
Summary
CCAAT enhancer binding factors (C/EBPs) regulate 17β-hydroxysteroid dehydrogenases (HSD17Bs). This study found HSD17B10 is specifically regulated by C/EBPβ isoforms in HepG2 cells, revealing new insights into HSD17B gene expression.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- 17β-hydroxysteroid dehydrogenases (HSD17Bs) are crucial enzymes in steroid metabolism, catalyzing C17 redox reactions.
- Fourteen mammalian HSD17B enzymes have been identified, each with distinct functions and regulatory mechanisms.
- Previous work indicated C/EBPβ regulates HSD17B8 in hepatocarcinoma cells.
Purpose of the Study:
- To investigate the potential regulation of HSD17B gene promoters by CCAAT enhancer binding factors (C/EBPs).
- To identify specific HSD17B genes regulated by C/EBPα and C/EBPβ isoforms.
- To elucidate the role of C/EBPβ isoforms in the transcriptional regulation of HSD17B10.
Main Methods:
- Bioinformatic analysis of 14 HSD17B 5'-flanking regions for C/EBP binding sites.
- Ectopic expression of C/EBPα and C/EBPβ in HepG2 cells.
- Gene reporter assays using wild-type and mutated HSD17B10 promoter constructs.
- Analysis of C/EBPβ isoform-specific effects on promoter activity.
Main Results:
- All HSD17B promoters, except HSD17B1, possess putative C/EBP binding sites.
- C/EBPα and C/EBPβ induced HSD17B11 expression; only C/EBPβ induced HSD17B10 expression.
- C/EBPβ specifically transactivated the HSD17B10 promoter.
- Specific C/EBPβ isoforms (LIP and LAP) differentially regulated HSD17B10 promoter activity, with CCAAT box mutation affecting LAP-induced transactivation.
Conclusions:
- HSD17B10 gene expression is significantly regulated by multiple C/EBPβ isoforms in HepG2 cells.
- The findings highlight the intricate role of transcription factor isoforms in controlling steroidogenic enzyme gene expression.
- This study provides a foundation for understanding the specific regulatory networks governing HSD17B family members.
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