Hypoxia inducible factor 1 alpha down-regulates type i collagen through Sp3 transcription factor in human chondrocytes
| Autor: | Duval, Elise, Bouyoucef, Mouloud, Leclercq, Sylvain, Baugé, Catherine, Boumediene, Karim |
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| Přispěvatelé: | Normandie Université (NU), Microenvironnement et Pathologies du Cartilage (BioConnecT), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Federation Hospitalo-Universitaire SURFACE |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
musculoskeletal diseases
hypoxia [SDV]Life Sciences [q-bio] collagen type I chondrocytes Gene Expression Regulation Developmental Cell Differentiation Genetic Therapy Hypoxia-Inducible Factor 1 alpha Subunit hypoxia-inducible factor 1 Collagen Type I alpha 1 Chain Sp3 Transcription Factor gene expression Humans Promoter Regions Genetic cartilage Cartilage Diseases Sp transcription factors |
| Zdroj: | International Union of Biochemistry and Molecular Biology Life International Union of Biochemistry and Molecular Biology Life, Wiley, 2016, pp.756-763. ⟨10.1002/iub.1539⟩ |
| DOI: | 10.1002/iub.1539⟩ |
| Popis: | Cartilage engineering is one challenging issue in regenerative medicine. Low oxygen tension or hypoxia inducible factor-1 (HIF-1α) gene therapy are promising strategies in the field of cartilage repair. Previously, we showed that hypoxia and its mediator HIF-1 regulate matrix genes expression (collagens and aggrecan). Here, we investigated the molecular mechanism involved in the regulation of type I collagen (COL1A1) by HIF-1 in human articular chondrocytes. We show that HIF-1α reduces COL1A1 transcription, through a distal promoter (-2300 to -1816 bp upstream transcription initiation site), containing two GC boxes that bind Sp transcription factors (Sp1/Sp3). Sp1 acts as a positive regulator but is not induced by HIF-1. COL1A1 inhibition caused by HIF-1 implies only Sp3, which accumulates and competes Sp1 binding on COL1A1 promoter. Additionally, Sp3 ectopic expression inhibits COL1A1, while Sp3 knockdown counteracts the downregulation of COL1A1 induced by HIF-1. In conclusion, we established a new regulatory model of COL1A1 regulation by HIF-1, and bring out its relationship with Sp3 transcription factor. In a fundamental level, these findings give insights in the mechanisms controlling COL1A1 gene expression. This may be helpful to improve strategies to impair type I collagen expression during chondrocyte differentiation for cartilage engineering. © 2016 IUBMB Life, 68(9):756-763, 2016. |
| Databáze: | OpenAIRE |
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