The microRNA-processing enzyme dicer maintains juxtaglomerular cells.
Juxtaglomerular cells are highly specialized myoepithelioid granulated cells located in the glomerular afferent arterioles. These cells synthesize and release renin, which distinguishes them from other cells. How these cells maintain their identity, restricted localization, and fate is unknown and is fundamental to the control of BP and homeostasis of fluid and electrolytes. Because microRNAs may control cell fate via temporal and spatial gene regulation, we generated mice with a conditional deletion of Dicer, the RNase III endonuclease that produces mature microRNAs in cells of the renin lineage. Deletion of Dicer severely reduced the number of juxtaglomerular cells, decreased expression of the renin genes (Ren1 and Ren2), lowered plasma renin concentration, and decreased BP. As a consequence of the disappearance of renin-producing cells, the kidneys developed striking vascular abnormalities and prominent striped fibrosis. We conclude that microRNAs maintain the renin-producing juxtaglomerular cells and the morphologic integrity and function of the kidney.
Sequeira-Lopez
Maria Luisa S
ML
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. msl7u@virginia.edu
Weatherford
Eric T
ET
Borges
Giulianna R
GR
Monteagudo
Maria C
MC
Pentz
Ellen S
ES
Harfe
Brian D
BD
Carretero
Oscar
O
Sigmund
Curt D
CD
Gomez
R Ariel
RA
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002452:Cell Count; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004722:Endoribonucleases / Q000235:genetics* / Q000378:metabolism*; D005355:Fibrosis; D017403:In Situ Hybridization; D007606:Juxtaglomerular Apparatus / Q000002:abnormalities / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D012079:Renal Circulation / Q000502:physiology; D012083:Renin / Q000097:blood*; D043244:Ribonuclease III
C543499:MIRN145a microRNA, mouse; D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D012083:Renin; D053487:DEAD-box RNA Helicases