Loss of miR-17~92 results in dysregulation of Cftr in nephron progenitors.
Am J Physiol Renal Physiol
; 316(5): F993-F1005, 2019 05 01.
Article
en En
| MEDLINE
| ID: mdl-30838872
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
/
Regulador de Conductancia de Transmembrana de Fibrosis Quística
/
MicroARNs
/
Nefronas
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Asunto de la revista:
FISIOLOGIA
/
NEFROLOGIA
Año:
2019
Tipo del documento:
Article