Abstract
Previous studies from 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. Our laboratory demonstrated increased expression of miRNAs regulating markers of inflammation in NHERF‐1 deficient mice and rat models. We hypothesized that loss of NHERF1 expression prevents salt‐sensitive hypertension due to changes in miRNA expression regulating Na‐transporters in renal tubules. To address this hypothesis, we analyzed the miRNA expression profile in 4mo and 24mo old FBN rats and 18mo old C57BL/6J wild‐type and NHERF1 knock‐out mice fed a normal salt or 8% salt diet (HSD). 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 cut‐off set at counts three times the SD of the negative control miRNA counts were considered for analysis. Counts from normal diet fed animals (n=8, 4M4F) were averaged together and considered as 1 to calculate changes in HSD animals. In 4‐mo old FBN rats 23 miRNAs significantly increased in HSD (miR196c, miR466b, miR144, and miR142‐5p), while miR547, miR375, and 6 others significantly decreased. In 24‐mo old FBN rats 30 miRNAs increased significantly in HSD (miR‐192, miRNA141, and miR21), while 10 miRNAs decreased significantly (miR328a and miR‐let‐7a and f). Similar results were observed in WT mice. However, in NHERF‐1 KO mice the miRNAs increased strongly regulate markers of inflammation. The data was confirmed by measuring the expression of down‐stream targets using western blotting and ELISA. These data may suggest that NHERF1 plays a major role in regulation of renal inflammation and salt‐sensitive hypertension.Support or Funding Information7R21AG047474‐03 NIH; R25AG047843‐NIH; 16GRNT31030019‐AHAThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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