期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 316, 期 5, 页码 F993-F1005出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00450.2018
关键词
cell cycle; cystic fibrosis transmembrane conductance regulator; differentiation; nephron progenitors; self-renewal
资金
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R00-DK-087922, R01-DK-103776]
- March of Dimes Basil O'Connor Starter Scholar Award
- NIDDK Diabetic Complications Consortium [DK-076169]
- American Society of Nephrology Ben J. Lipps Research Fellowship Program
- Research Advisory Committee of Children's Hospital of Pittsburgh
- National Institute of General Medical Sciences [GM-115836]
- NIDDK [DK-102843, T32-DK-061296]
We have previously demonstrated that loss of miR-17 similar to 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 similar to 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.
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