Hnf-1ß transcription factor is an early hif-1α-independent marker of epithelial hypoxia and controls renal repair.
PLoS One
; 8(5): e63585, 2013.
Article
en En
| MEDLINE
| ID: mdl-23704921
ABSTRACT
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-1ß 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-1ß from 1 to 24 hours, independently of the hypoxia-inducible factor Hif-1α. When prolonged, hypoxia induced Hnf-1ß down-regulation while normoxia led to Hnf-1ß normalization. Last, Hnf-1ß 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-1ß 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Epiteliales
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Factor Nuclear 1-beta del Hepatocito
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Riñón
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2013
Tipo del documento:
Article