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Role of transcription factor hepatocyte nuclear factor-1 beta in polycystic kidney disease

机译:转录因子肝细胞核因子-1β在多囊肾疾病中的作用

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Hepatocyte nuclear factor-1 beta (HNF-1 beta) is a DNA-binding transcription factor that is essential for normal kidney development. Mutations of HNF1B in humans produce cystic kidney diseases, including renal cysts and diabetes, multicystic dysplastic kidneys, glomerulocystic kidney disease, and autosomal dominant tubulointerstitial kidney disease. Expression of HNF1B is reduced in cystic kidneys from humans with ADPKD, and HNF1B has been identified as a modifier gene in PKD. Genome-wide analysis of chromatin binding has revealed that HNF-1 beta directly regulates the expression of known PKD genes, such as PKHD1 and PKD2, as well as genes involved in PKD pathogenesis, including cAMP-dependent signaling, renal fibrosis, and Wnt signaling. In addition, a role of HNF-1 beta in regulating the expression of noncoding RNAs (microRNAs and long noncoding RNAs) has been identified. These findings indicate that HNF-1 beta regulates a transcriptional and post-transcriptional network that plays a central role in renal cystogenesis.
机译:肝细胞核因子-1β(HNF-1β)是一种DNA结合转录因子,对于正常的肾发育至关重要。人类HNF1B的突变产生囊性肾脏疾病,包括肾囊肿和糖尿病,多象症发育性肾脏,肾小球囊肿肾病和常染色体显性细胞间肾病。 HNF1b的表达降低了来自具有ADPKD的人类的囊性肾脏,HNF1b已被鉴定为PKD中的改性剂基因。染色质结合的基因组分析表明,HNF-1β直接调节已知的PKD基因的表达,例如PKHD1和PKD2,以及参与PKD发病机制的基因,包括CAMP依赖性信号,肾纤维化和WNT信号传导。此外,已经鉴定了HNF-1β在调节非定量RNA(MicroRNA和长期非编码RNA)的表达方面的作用。这些发现表明,HNF-1β调节在肾囊泡中发挥着核心作用的转录和转录后网络。

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