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KIDNEY DISEASE

Metabolic reprogramming in polycystic kidney disease explained by super-enhancers and CDK7: new therapeutic targets?

Nature Metabolism volume 2, pages 659–660 (2020)Cite this article

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In this issue of Nature Metabolism, Mi and colleagues provide evidence that super-enhancers play a critical role in autosomal-dominant polycystic kidney disease (ADPKD) and show that CDK7 targeting provides a novel therapeutic option.

ADPKD is the most common inherited nephropathy, accounting for 10% of all cases of end-stage renal disease worldwide2. ADPKD is a progressive disorder characterized by the formation of numerous cysts in both kidneys and frequently in the liver bile ducts2. The cysts are hollow, fluid-filled formations enclosed by a single layer of epithelia. They affect a small number of nephrons. However, their gradual expansion compresses the normal renal parenchyma and causes inflammation, fibrosis and eventually organ failure2. The disease is due to loss-of-function mutations in either the PKD1 or the PKD2 gene, both of which encode large membrane proteins called polycystins.

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Fig. 1: Rearrangement of the SE landscape may account for metabolic reprogramming in ADPKD.

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Acknowledgements

The authors are grateful to A. Mondino and D. Gabellini for critically reading the manuscript. A.B. and L.C. are supported by the Italian Ministry of Health, the PKD Foundation and the Italian Association for Research on Cancer (AIRC).

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  1. Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Laura Cassina & Alessandra Boletta

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  1. Laura Cassina
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  2. Alessandra Boletta
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Correspondence to Alessandra Boletta.

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Competing interests

A.B. is a co-inventor on two patents for the targeting of cell metabolism in ADPKD.

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Cassina, L., Boletta, A. Metabolic reprogramming in polycystic kidney disease explained by super-enhancers and CDK7: new therapeutic targets?. Nat Metab 2, 659–660 (2020). https://doi.org/10.1038/s42255-020-0232-7

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  • DOI: https://doi.org/10.1038/s42255-020-0232-7

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