Regulation of WNK1 expression by miR-192 and aldosterone.
WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP. A combination of promoters, enhancers, repressors, and insulators regulate WNK1 expression, but whether microRNAs also modulate WNK1 expression is unknown. Here, computational analysis revealed the presence of a target sequence for miR-192 and miR-215 at the same site in the 3' untranslated region of the ubiquitous L- and the kidney-specific KS-WNK1. We functionally validated this target sequence by transient transfection and reporter assays. Although we observed expression of both miRs along the distal nephron, only miR-192 regulated endogenous WNK1 ex vivo. Furthermore, a potassium load, sodium depletion, and aldosterone infusion each significantly reduced miR-192 expression in the kidney. Taken together, these results suggest a miR-driven mechanism of gene regulation by aldosterone and a role for miR-192 in the regulation of sodium and potassium balance in the kidney.
Elvira-Matelot
Emilie
E
INSERM U970, Paris Centre for Cardiovascular Research, Paris, France.
Zhou
Xiao-ou
XO
Farman
Nicolette
N
Beaurain
Geneviève
G
Henrion-Caude
Alexandra
A
Hadchouel
Juliette
J
Jeunemaitre
Xavier
X
D020413:3' Untranslated Regions; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004285:Dogs; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D011188:Potassium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012982:Sodium, Dietary / Q000378:metabolism; D000076204:WNK Lysine-Deficient Protein Kinase 1
D020413:3' Untranslated Regions; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; C539618:Mirn192 microRNA, mouse; D012982:Sodium, Dietary; D000450:Aldosterone; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498744:Wnk1 protein, mouse; D011188:Potassium
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