Hippo signaling-a central player in cystic kidney disease?

Pediatr Nephrol. 2020 Jul;35(7):1143-1152. doi: 10.1007/s00467-019-04299-3. Epub 2019 Jul 11.


Cystic transformation of kidney tissue is a key feature of various disorders including autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), and disorders of the nephronophthisis spectrum (NPH). While ARPKD and NPH typically affect children and adolescents, pediatric onset of ADPKD is less frequently found. While both ADPKD and ARPKD are characterized by formation of hundreds of cysts accompanied by hyperproliferation of tubular epithelia with massive renal enlargement, NPH patients usually show kidneys of normal or reduced size with cysts limited to the corticomedullary border. Recent results suggest the hippo pathway to be a central regulator at the crossroads of the renal phenotype in both diseases. Hippo signaling regulates organ size and proliferation by keeping the oncogenic transcriptional co-activators Yes associated protein 1 (YAP) and WW domain containing transcription regulator 1 (TAZ) in check. Once this inhibition is released, nuclear YAP/TAZ interacts with TEAD family transcription factors and the consecutive transcriptional activation of TEA domain family members (TEAD) target genes mediates an increase in proliferation. Here, we review the current knowledge on the impact of NPHP and ADPKD mutations on Hippo signaling networks. Furthermore, we provide an outlook towards potential future therapeutic strategies targeting Hippo signaling to alleviate cystic kidney disease.

Keywords: ADPKD; Cystic kidney disease; Hippo; NPH; TAZ; YAP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Humans
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Polycystic Kidney, Autosomal Dominant / pathology
  • Polycystic Kidney, Autosomal Recessive / metabolism*
  • Polycystic Kidney, Autosomal Recessive / pathology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism


  • Adaptor Proteins, Signal Transducing
  • Transcription Factors
  • YAP1 protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases