New insights into the role of HNF-1β in kidney (patho)physiology

Pediatr Nephrol. 2019 Aug;34(8):1325-1335. doi: 10.1007/s00467-018-3990-7. Epub 2018 Jul 1.


Hepatocyte nuclear factor-1β (HNF-1β) is an essential transcription factor that regulates the development and function of epithelia in the kidney, liver, pancreas, and genitourinary tract. Humans who carry HNF1B mutations develop heterogeneous renal abnormalities, including multicystic dysplastic kidneys, glomerulocystic kidney disease, renal agenesis, renal hypoplasia, and renal interstitial fibrosis. In the embryonic kidney, HNF-1β is required for ureteric bud branching, initiation of nephrogenesis, and nephron segmentation. Ablation of mouse Hnf1b in nephron progenitors causes defective tubulogenesis, whereas later inactivation in elongating tubules leads to cyst formation due to downregulation of cystic disease genes, including Umod, Pkhd1, and Pkd2. In the adult kidney, HNF-1β controls the expression of genes required for intrarenal metabolism and solute transport by tubular epithelial cells. Tubular abnormalities observed in HNF-1β nephropathy include hyperuricemia with or without gout, hypokalemia, hypomagnesemia, and polyuria. Recent studies have identified novel post-transcriptional and post-translational regulatory mechanisms that control HNF-1β expression and activity, including the miRNA cluster miR17 ∼ 92 and the interacting proteins PCBD1 and zyxin. Further understanding of the molecular mechanisms upstream and downstream of HNF-1β may lead to the development of new therapeutic approaches in cystic kidney disease and other HNF1B-related renal diseases.

Keywords: Development; Hepatocyte nuclear factor-1β; Ion transport; Metabolism; Polycystic kidney disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Down-Regulation
  • Gene Expression Regulation, Developmental*
  • Hepatocyte Nuclear Factor 1-beta / genetics
  • Hepatocyte Nuclear Factor 1-beta / metabolism*
  • Humans
  • Hydro-Lyases / metabolism
  • Kidney Diseases, Cystic / blood
  • Kidney Diseases, Cystic / genetics*
  • Kidney Diseases, Cystic / pathology
  • Kidney Diseases, Cystic / urine
  • Kidney Tubules / abnormalities*
  • Kidney Tubules / pathology
  • MicroRNAs / metabolism
  • Mutation
  • RNA, Long Noncoding
  • Receptors, Cell Surface / genetics
  • TRPP Cation Channels / genetics
  • Uromodulin / genetics
  • Urothelium / abnormalities*
  • Urothelium / pathology
  • Zyxin / metabolism


  • HNF1B protein, human
  • MIR17HG, human
  • MicroRNAs
  • PKHD1 protein, human
  • RNA, Long Noncoding
  • Receptors, Cell Surface
  • TRPP Cation Channels
  • UMOD protein, human
  • Uromodulin
  • ZYX protein, human
  • Zyxin
  • polycystic kidney disease 2 protein
  • Hepatocyte Nuclear Factor 1-beta
  • Hydro-Lyases
  • pterin-4a-carbinolamine dehydratase