Hnf-1β transcription factor is an early hif-1α-independent marker of epithelial hypoxia and controls renal repair
| Autor: | Jean-Loup Bascands, Audrey Casemayou, Claire Cartery, Gilbert J. Fournié, Nicolas Mayeur, Dominique Chauveau, Anne-Laure Pageaud, Claire Courtellemont, Ivan Tack, Stanislas Faguer, Joost P. Schanstra |
|---|---|
| Přispěvatelé: | Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de référence des maladies rénales rares, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Anesthésie - Réanimation, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service des explorations physiologiques, Simon, Marie Francoise, Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Référence du sud-Ouest des maladies rénales rares [CHU Toulouse] (SODARE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pôle Anesthésie Réanimation [CHU de Toulouse], Service des Explorations Fonctionnelles Physiologiques [CHU Toulouse] |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Pathology
Anatomy and Physiology 030232 urology & nephrology Kidney development lcsh:Medicine Gene Expression Kidney Kidney Tubules Proximal Mice 0302 clinical medicine Gene expression Molecular Cell Biology Homeostasis SOCS3 lcsh:Science Epithelial cell differentiation Cellular Stress Responses Regulation of gene expression 0303 health sciences Multidisciplinary Acute Kidney Injury Cell Hypoxia Endocytosis Cell biology medicine.anatomical_structure Nephrology Medicine Female Cellular Types Research Article medicine.medical_specialty Mesenchyme Biology Shock Hemorrhagic Cell Line 03 medical and health sciences medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger Transcription factor 030304 developmental biology Hepatocyte Nuclear Factor 1-beta Wound Healing lcsh:R Epithelial Cells Prolyl-Hydroxylase Inhibitors Hypoxia-Inducible Factor 1 alpha Subunit Mice Inbred C57BL Disease Models Animal Gene Expression Regulation lcsh:Q Acute Renal Failure Physiological Processes Biomarkers |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2013, 8 (5), pp.e63585. ⟨10.1371/journal.pone.0063585⟩ PLoS ONE, 2013, 8 (5), pp.e63585. ⟨10.1371/journal.pone.0063585⟩ PLoS ONE, Vol 8, Iss 5, p e63585 (2013) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0063585⟩ |
| Popis: | International audience; Epithelial repair following acute kidney injury (AKI) requires epithelial-mesenchyme-epithelial cycling associated with transient re-expression of genes normally expressed during kidney development as well as activation of growth factors and cytokine-induced signaling. In normal kidney, the Hnf-1β transcription factor drives nephrogenesis, tubulogenesis and epithelial homeostasis through the regulation of epithelial planar cell polarity and expression of developmental or tubular segment-specific genes. In a mouse model of ischemic AKI induced by a 2-hours hemorrhagic shock, we show that expression of this factor is tightly regulated in the early phase of renal repair with a biphasic expression profile (early down-regulation followed by transient over-expression). These changes are associated to tubular epithelial differentiation as assessed by KSP-cadherin and megalin-cubilin endocytic complex expression analysis. In addition, early decrease in Hnf1b expression is associated with the transient over-expression of one of its main target genes, the suppressor of cytokine signaling Socs3, which has been shown essential for renal repair. In vitro, hypoxia induced early up-regulation of Hnf-1β from 1 to 24 hours, independently of the hypoxia-inducible factor Hif-1α. When prolonged, hypoxia induced Hnf-1β down-regulation while normoxia led to Hnf-1β normalization. Last, Hnf-1β down-regulation using RNA interference in HK-2 cells led to phenotype switch from an epithelial to a mesenchyme state. Taken together, we showed that Hnf-1β may drive recovery from ischemic AKI by regulating both the expression of genes important for homeostasis control during organ repair and the state of epithelial cell differentiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|