ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO985

Observation of Circadian Clock Genes Associated With Rhythmic Variation of the Aldosterone Signaling Pathway

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Thelwell, Ryanne Simone, University of Florida, Gainesville, Florida, United States
  • Gumz, Michelle L., University of Florida, Gainesville, Florida, United States
  • Crislip, G. Ryan, University of Florida, Gainesville, Florida, United States
  • Douma, Lauren G., University of Florida, Gainesville, Florida, United States
Background

Circadian rhythms regulate several physiological functions. In renal function, blood pressure is circadian regulated. The renin-angiotensin-aldosterone-system (RAAS) plays a major role in blood pressure homeostasis. Chronic kidney disease is primarily a disease of aging. The impact of circadian clock gene function with age requires further study. Variations in the rhythmically expressed genes (REGs) of this study play a role in the loss of the circadian nature of the aldosterone signaling pathway in older mice.

Methods

6 month, 18 month, and 27 month old male mice from National Institute on Aging (NIA) were used to observe molecular clock transcriptional output after subsequent light/dark cycles.RNA sequencing performed on hypothalamus, kidney, lung, gastrocnemius, adrenal gland, and heart tissue. Data from RNA sequencing was processed using R software and circadian rhythmicity was analyzed using the cosinor model available in the diffCircadian software. REGs observed for their effect in aldosterone signaling pathway include Scnn1a, Scnn1b, Scnn1g, Nr3c1, Nr3c2, Hsp90,Atp1a1, Slc9a3, Slc12a1, Slc12a3, Prkca, Mapk1, Kras, Map2k1, Raf1, Pik3ca, Pdk1, Nedd4L, Sahh, Hsd11b1 and Hsd11b2.

Results

Kras expression rhythmically circadian in young and aged mice (p<0.05) but not at all in old mice (p=0.943). Pik3ca expression was rhythmically circadian in young, aged mice (p<0.05) but not at all in old mice (p=0.403). There was also a significant drop in basal expression levels (125 and 124 to 97 for young, aged, and old respectively). Most gene expression rhythmically circadian in young and aged mice (supported by lowest p values).

Conclusion

The decline in transcriptional output of rhythmically expressed genes throughout each tissue with age suggest a loss of circadian regulation. Variation in REGs' transcription observed in the aldosterone signaling pathway support loss of circadian patterns with increasing age in mice.