Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation.

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Gianluca AguiariLaura del Senno

Abstract

In autosomal dominant polycystic kidney disease (ADPKD), renal cyst development and enlargement, as well as cell growth, are associated with alterations in several pathways, including cAMP and activator protein 1 (AP1) signalling. However, the precise mechanism by which these molecules stimulate cell proliferation is not yet fully understood. We now show by microarray analysis, luciferase assay, mutagenesis, and chromatin immunoprecipitation that CREB and AP1 contribute to increased expression of the amphiregulin gene, which codifies for an epidermal growth factor-like peptide, in ADPKD cystic cells, thereby promoting their cell growth. Increased amphiregulin (AR) expression was associated with abnormal cell proliferation in both PKD1-depleted and -mutated epithelial cells, as well as primary cystic cell lines isolated from ADPKD kidney tissues. Consistently, normal AR expression and proliferation were re-established in cystic cells by the expression of a mouse full-length PC1. Finally, we show that anti-AR antibodies and inhibitors of AP1 are able to reduce cell proliferation in cystic cells by reducing AR expression and EGFR activity. AR can therefore be considered as one of the key activators of the growth of human ADPKD cys...Continue Reading

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Citations

Feb 23, 2013·American Journal of Nephrology·Gianluca AguiariLaura Del Senno
Jan 28, 2014·Seminars in Cell & Developmental Biology·Carmen Berasain, Matías A Avila
Jun 4, 2014·The Journal of Clinical Investigation·Peter C Harris, Vicente E Torres
Nov 5, 2013·Biochemical and Biophysical Research Communications·Anna BononGianluca Aguiari
Dec 2, 2014·Translational Research : the Journal of Laboratory and Clinical Medicine·Wells B LaRiviereVicente E Torres
Jun 10, 2016·Clinical and Experimental Nephrology·Lucia de StephanisGianluca Aguiari
May 18, 2016·Journal of Molecular Cell Biology·Vijayakumar R KakadeReena Rao
Nov 28, 2014·Scientific Reports·Karothu Durga PrasadTayur N Guru Row
Jan 13, 2018·Journal of Cellular Physiology·Lucia de StephanisGianluca Aguiari
Jan 21, 2016·World Journal of Nephrology·Alessandra MangoliniGianluca Aguiari
Nov 16, 2017·Current Opinion in Organ Transplantation·Caroline Lamarche, Megan K Levings
Dec 18, 2013·Journal of the American Society of Nephrology : JASN·Vicente E Torres, Peter C Harris
Jul 5, 2016·Nature Reviews. Nephrology·Laura R HarskampEsther Meijer
Jun 6, 2013·Current Opinion in Nephrology and Hypertension·Olivier Devuyst, Vicente E Torres
May 6, 2017·Frontiers in Pediatrics·William E Sweeney, Ellis D Avner
Jan 24, 2019·Mediators of Inflammation·Sandra Rayego-MateosMarta Ruiz-Ortega
Oct 24, 2019·BioMed Research International·Yan TangZuocheng Wang
Feb 20, 2018·Molecular Cancer·Aniello CerratoAngela Celetti
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May 1, 2019·The Journal of Pathology·Chiara FormicaDorien Jm Peters
Dec 13, 2019·Cellular Signalling·Mitchell I ParkerErica A Golemis
Oct 27, 2021·Journal of Cellular Physiology·Siddharth S SinghRajiv Kumar

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