Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Cell Signal. 2020 Jul;71:109568. doi: 10.1016/j.cellsig.2020.109568. Epub 2020 Feb 14.
Hepatocyte nuclear factor-1β (HNF-1β) 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-1β 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-1β in regulating the expression of noncoding RNAs (microRNAs and long noncoding RNAs) has been identified. These findings indicate that HNF-1β regulates a transcriptional and post-transcriptional network that plays a central role in renal cystogenesis.
肝细胞核因子-1β（HNF-1β）是一种 DNA 结合转录因子，对于正常肾脏发育至关重要。人类 HNF1B 的突变会导致囊性肾脏疾病，包括肾囊肿和糖尿病、多囊性发育不良肾脏、肾小球囊性病和常染色体显性遗传性肾小管间质性肾病。在 ADPKD 患者的囊性肾脏中，HNF1B 的表达减少，并且 HNF1B 已被确定为 PKD 的修饰基因。染色质结合的全基因组分析表明，HNF-1β 可直接调节已知的 PKD 基因（如 PKHD1 和 PKD2）以及 PKD 发病机制相关基因（包括 cAMP 依赖性信号转导、肾脏纤维化和 Wnt 信号转导）的表达。此外，还确定了 HNF-1β 在调节非编码 RNA（microRNAs 和长非编码 RNA）表达中的作用。这些发现表明，HNF-1β 调节了一个转录和转录后网络，该网络在肾脏囊肿发生中起着核心作用。
