Age‐dependent Changes in miRNA Profile in F344 rat and C57BL/6J mice: Role of sodium hydrogen exchanger regulatory factor‐1 (NHERF1)

Our laboratory demonstrated decreased NHERF1 expression in aging F344. Loss of NHERF1 expression prevented dopamine‐dependent inhibition of NKA in renal PTCs from aged F344. We hypothesized that loss of NHERF1 expression in aged F344 rats is due to changes in miRNA expression. To address this hypothesis we analyzed the miRNA expression profile in 4mo and 22mo old F344 rats and 2 and 18mo old C57BL/6J wild‐type and NHERF1 knock‐out mice. Total RNA from kidney cortex was isolated using Trizol (miRVana, Ambion) and miRNA profile was analyzed using kits and software from Nanostring. The top 100 miRNAs with 25% counts above the negative miRNA counts were considered for analysis. Counts from young animals (n=4, 2M2F) were averaged together and considered as 1. Counts from old animals (n=4, 2M2F) were calculated as fold change. In F344 rats 10 miRNAs increased with age (miR29a, miR29b, miR29c, and miR21), while miR96 and miR328a decreased. In WT‐ mice 51 miRNAs increased with age (miR‐let‐7g, b, and d; and miR22), while 28 miRNAs decreased (miR21 and miR‐let‐7e). In NHERF1‐KO mice 31 miRNAs increased with age (miRNA21, miR29a, miR29b, and miR29c), while 22 miRNAs decreased (miR‐let‐7a, miR‐let‐7b, miR‐let‐7c, and miR24). Our results suggest that miRNAs that regulate inflammation increased with age in both F344 rats and NHERF1‐KO mice. Interestingly, these miRNAs decreased in WT mice. These data may explain the mechanisms of increased renal inflammation in NHERF1 deficient models of hypertension. Support or Funding Information 7R21AG047474‐03 NIH R25AG047843‐NIH 16GRNT31030019‐AHA This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .