Loss of miR-17~92 results in dysregulation of Cftr in nephron progenitors.

Autor:	Phua YL; Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.; Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Chen KH; Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.; Department of Biological Sciences, Carnegie Mellon University , Pittsburgh, Pennsylvania., Hemker SL; Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.; Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Marrone AK; Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.; Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Bodnar AJ; Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.; Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Liu X; Department of Cell Biology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Clugston A; Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.; Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.; Department of Developmental Biology and Department of Computational and Systems Biology, Pittsburgh Center for Evolutionary Biology and Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Kostka D; Department of Developmental Biology and Department of Computational and Systems Biology, Pittsburgh Center for Evolutionary Biology and Medicine, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Butterworth MB; Department of Cell Biology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania., Ho J; Rangos Research Center, UPMC Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania.; Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2019 May 01; Vol. 316 (5), pp. F993-F1005. Date of Electronic Publication: 2019 Mar 06.
DOI:	10.1152/ajprenal.00450.2018
Abstrakt:	We have previously demonstrated that loss of miR-17~92 in nephron progenitors in a mouse model results in renal hypodysplasia and chronic kidney disease. Clinically, decreased congenital nephron endowment because of renal hypodysplasia is associated with an increased risk of hypertension and chronic kidney disease, and this is at least partly dependent on the self-renewal of nephron progenitors. Here, we present evidence for a novel molecular mechanism regulating the self-renewal of nephron progenitors and congenital nephron endowment by the highly conserved miR-17~92 cluster. Whole transcriptome sequencing revealed that nephron progenitors lacking this cluster demonstrated increased Cftr expression. We showed that one member of the cluster, miR-19b , is sufficient to repress Cftr expression in vitro and that perturbation of Cftr activity in nephron progenitors results in impaired proliferation. Together, these data suggest that miR-19b regulates Cftr expression in nephron progenitors, with this interaction playing a role in appropriate nephron progenitor self-renewal during kidney development to generate normal nephron endowment.
Databáze:	MEDLINE
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