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Kidney Week

Abstract: SA-PO729

Chloride Channel Accessory 1 Protein Could Be a Novel Regulatory Factor in Aging-Related Changes in the Kidney

Session Information

  • Geriatric Nephrology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Geriatric Nephrology

  • 1100 Geriatric Nephrology

Authors

  • Donati, Andrew, Univeristy of Texas Health, San Antonio, Texas, United States
  • Lee, Hak Joo, University of Texas Health, San Antonio, Texas, United States
  • Salmon, Adam, Univeristy of Texas Health, San Antonio, Texas, United States
  • Ghosh-Choudhury, Goutam, University of Texas Health, San Antonio, Texas, United States
  • Ross, Corinna, Texas A&M San Antonio, San Antonio, Texas, United States
  • Tardif, Suzette D., Texas Biomedical Research Institute, San Antonio, Texas, United States
  • Kasinath, Balakuntalam S., Univeristy of Texas Health, San Antonio, Texas, United States
Background

We have reported that aging induces kidney fibrosis, albuminuria and impairs clearance function in mice (Sataranatarajan K, Aging Cell, 2012). The underlying mechanisms are not well understood. In the current study, we took an unbiased discovery approach to identify potentially novel mechanisms.

Methods

We performed RNA Seq on renal cortical samples from C57BL6 male young mice (5 months old, n=4) and old mice (30 months old, n=3). Next, we directly verified changes in mRNAs that showed the maximum increase by performing qRT-PCR. We studied changes in renal cortical chloride channel accessory protein 1 (CLCA1) protein expression by immunoblotting (male and female young and old mice, n=6 to 10 per group). To study if changes found in mice were evolutionarily conserved, we studied kidney tissue from non-human primate marmosets (young 3 yrs of age, old 16 yrs of age, male and female, n=8-10 per group).

Results

On RNA Seq, we found CLCA1 as one of the mRNAs that showed most significant increase in old vs. young mice (p=7.6E-27). We performed qRT-PCR to directly test the status of CLCA1 mRNA; we confirmed a 10-fold increase in renal cortex of old male mice compared to young mice. Immunoblotting showed a 2-fold increase in CLCA1 protein in renal cortex of old male mice but not old female mice. We have reported that renal hydrogen sulfide (H2S) generation is reduced in aging mice; administration of sodium hydrosulfide (NaHS, a source of H2S) to 19 month-old mice for 5 months ameliorates aging-related kidney changes in mice (Lee HJ, GeroScience, 2018). NaHS administration decreased renal cortical CLCA1 expression by 40% compared to untreated Control old mice. On immunohistochemistry CLCA1 was expressed mostly in the tubules in young marmosets. Renal cortical CLCA1 expression was increased 2-fold in old male and female marmosets.

Conclusion

Increase in renal cortical CLCA1 expression correlates with aging-related kidney dysfunction in male mice; it appears to be evolutionarily conserved from mice to marmosets. CLCA1 activates Ca++-dependent chloride channel TMEM16A that is expressed in kidney proximal tubules and podocytes. Mechanisms by which CLCA1 contributes to renal aging need to be explored.

Funding

  • Veterans Affairs Support