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Hippo signaling—a central player in cystic kidney disease?

  • Roman-Ulrich MüllerEmail author
  • Bernhard SchermerEmail author
Review

Abstract

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

Cystic kidney disease ADPKD NPH Hippo YAP TAZ 

Notes

Acknowledgments

We thank Petra Kleinwächter (MedizinFotoKöln) for excellent assistance designing the figure.

Funding

R.-U.M. was supported by funding from the Ministry of Culture and Science Northrine-Westfalia in the framework of the Nachwuchsgruppen, NRW program. B.S. was funded by the Deutsche Forschungsgemeinschaft (SCHE 1562/6) and by the German Federal Ministry for Education and Research (NEOCYST consortium FKZ 01GM1515E).

Compliance with ethical standards

Conflict of interest

R.-U.M. received honoraria for counselling and scientific lectures and the Dept. II of Internal Medicine was supported by research funding from Otsuka Pharmaceutical.

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Copyright information

© IPNA 2019

Authors and Affiliations

  1. 1.Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital of CologneUniversity of CologneCologneGermany
  2. 2.Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD)University of CologneCologneGermany
  3. 3.Systems Biology of Ageing CologneUniversity of CologneCologneGermany

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