Hnf-1β transcription factor is an early hif-1α-independent marker of epithelial hypoxia and controls renal repair.
Hnf-1β transcription factor is an early hif-1α-independent marker of epithelial hypoxia and controls renal repair.
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DOI：
10.1371/journal.pone.0063585
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chauveau D
中科院分区：
文献类型：
--
作者：
Faguer S;Mayeur N;Casemayou A;Pageaud AL;Courtellemont C;Cartery C;Fournie GJ;Schanstra JP;Tack I;Bascands JL;Chauveau D
急性肾损伤（阿基）后的上皮修复需要上皮-间充质-上皮循环，其与在肾脏发育期间正常表达的基因的瞬时再表达以及生长因子和精氨酸诱导的信号传导的活化相关。在正常肾脏中，Hnf-1β转录因子通过调节上皮平面细胞极性和发育或肾小管节段特异性基因的表达来驱动肾发生、肾小管发生和上皮稳态。在由2小时出血性休克诱导的缺血性阿基小鼠模型中，我们表明该因子的表达在肾脏修复的早期阶段受到严格调控，具有双相表达谱（早期下调，随后是短暂的过度表达）。通过KSP-cadherin和megalin-cubilin内吞复合物表达分析评估，这些变化与肾小管上皮细胞分化相关。此外，Hnf 1b表达的早期降低与其主要靶基因之一的瞬时过表达相关，该基因是细胞因子信号传导抑制因子Socs 3，其已被证明对肾修复至关重要。在体外，缺氧诱导Hnf-1β在1 - 24小时早期上调，不依赖于缺氧诱导因子Hif-1α。当缺氧时间延长时，Hnf-1β表达下调，而常氧则使Hnf-1β恢复正常。最后，在HK-2细胞中使用RNA干扰下调Hnf-1β导致表型从上皮状态转变为间充质状态。综上所述，我们发现Hnf-1β可能通过调节器官修复过程中对稳态控制重要的基因表达和上皮细胞分化状态来促进缺血性阿基的恢复。
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.
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影响因子：
19.6
作者：
Price, Peter M.;Safirstein, Robert L.;Megyesi, Judit
通讯作者：
Megyesi, Judit
影响因子：
8.8
作者：
Mayeur, Nicolas;Minville, Vincent;Tack, Ivan
通讯作者：
Tack, Ivan
DOI：
10.1006/bbrc.2000.3762
发表时间：
2000-11-11
影响因子：
3.1
作者：
Dey, BR;Furlanetto, RW;Nissley, P
通讯作者：
Nissley, P
影响因子：
4.6
作者：
Lokmane, Ludmilla;Heliot, Claire;Cereghini, Silvia
通讯作者：
Cereghini, Silvia
影响因子：
5.3
作者：
Leu, JI;Crissey, MAS;Tau, R
通讯作者：
Tau, R