HIF1 transcription factor regulates laminin-332 expression and keratinocyte migration

Autor: Roser Buscà, Francesca Cianfarani, Gilles Ponzio, Séverine Augier, Giorgos Fitsialos, Guerrino Meneguzzi, Jacques Pouysségur, Edurne Berra, Teresa Odorisio, Thierry Virolle, Isabelle Bourget, Amandine Ginouvès, Roger Rezzonico
Přispěvatelé: Biologie et physiopathologie cutanées : expression génique, signalisation et thérapie, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR50, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Laboratory Molecular and Cellular Biology (IDI-IRCCS), IDI-IRCCS, Cell Biology and Stem Cells Unit (CICbioGUNE), Technologic Park of Bizkaia, Immunologie cellulaire et moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et biothérapie: cellules souches, développement et cancer, Institute of Developmental Biology and Cancer (IBDC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2008
Předmět:
Keratinocytes
Male
[SDV]Life Sciences [q-bio]
Molecular Sequence Data
[SDV.CAN]Life Sciences [q-bio]/Cancer
03 medical and health sciences
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Downregulation and upregulation
Laminin
Cell Movement
medicine
Gene silencing
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Keratinocyte migration
Promoter Regions
Genetic
Transcription factor
PI3K/AKT/mTOR pathway
ComputingMilieux_MISCELLANEOUS
Cells
Cultured
030304 developmental biology
0303 health sciences
Wound Healing
biology
integumentary system
Base Sequence
Cell Biology
Hypoxia-Inducible Factor 1
alpha Subunit
Cell biology
Mice
Inbred C57BL
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
biology.protein
Hypoxia-Inducible Factor 1
Keratinocyte
Wound healing
Cell Adhesion Molecules
Signal Transduction
Zdroj: Europe PubMed Central
Journal of Cell Science
Journal of Cell Science, Company of Biologists, 2008, 121 (Pt 18), pp.2992-3001. ⟨10.1242/jcs.029256⟩
Journal of Cell Science, Company of Biologists, 2008, 121 (18), pp.2992-3001. ⟨10.1242/jcs.029256⟩
ISSN: 0021-9533
1477-9137
Popis: Epidermal wound repair is a complex process involving the fine orchestrated regulation of crucial cell functions, such as proliferation, adhesion and migration. Using an in vitro model that recapitulates central aspects of epidermal wound healing, we demonstrate that the transcription factor HIF1 is strongly stimulated in keratinocyte cultures submitted to mechanical injury. Signals generated by scratch wounding stabilise the HIF1alpha protein, which requires activation of the PI3K pathway independently of oxygen availability. We further show that upregulation of HIF1alpha plays an essential role in keratinocyte migration during the in vitro healing process, because HIF1alpha inhibition dramatically delays the wound closure. In this context, we demonstrate that HIF1 controls the expression of laminin-332, one of the major epithelial cell adhesion ligands involved in cell migration and invasion. Indeed, silencing of HIF1alpha abrogates injury-induced laminin-332 expression, and we provide evidence that HIF1 directly regulates the promoter activity of the laminin alpha3 chain. Our results suggest that HIF1 contributes to keratinocyte migration and thus to the re-epithelialisation process by regulating laminin-332.
Databáze: OpenAIRE
Externí odkaz: