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Kidney Week

Abstract: FR-PO978

Association of Aging-Related Decline in Quinolinate Phosphoribosyl Transferase Expression and Expression of Profibrotic Genes

Session Information

  • CKD: Pathobiology - I
    November 04, 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

  • Saade, Marie Christelle, The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States
  • Clark, Amanda J., The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States
  • Mendoza Flores, Brenda, The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States
  • Parikh, Samir M., The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States

Group or Team Name

  • Parikh Lab
Background

De novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway was shown to be impaired in chronic kidney disease (CKD) and routine aging with a particular role for quinolinate phosphoribosyl transferase (QPRT), a bottleneck enzyme of the de novo NAD+ pathway. Yet, it is still undetermined whether QPRT and generalized NAD+ biosynthetic suppression is simply correlated with CKD progression or whether loss of these pathways may drive disease progression. Therefore, we investigated aged QPRT deficient mice.

Methods

Custom QPRT +/- were bred and aged under routine care on a normal chow diet. Expression of QPRT and fibrotic genes TGFB and COL1A1 was measured in QPRT +/- (HT) and wildtype (WT) littermates at an 8-week-old “young” time point and a 72-week-old “aged” time point. Serum blood urea nitrogen (BUN) and creatinine were measured using a commercial kit and capillary electrophoresis respectively.

Results

QPRT expression significantly declined with age in HT and WT mice. Old WT mice expressed less QPRT than young HT mice. In the aged group, TGFB expression was significantly higher in aged HT mice despite unchanged BUN and creatinine. There was no significant difference between young and old HT vs WT COL1A1 gene expression, though expression trended higher in aged HT. (Figure 1) TGFB expression significantly correlated with QPRT expression in both old and young mice populations (Figure 2).

Conclusion

Our data demonstrate a suppression of kidney QPRT expression with age. QPRT reduction may exacerbate fibrotic gene expression even in the absence of overt kidney disease.

Funding

  • Other NIH Support