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Abstract: FR-PO174

Following AKI, Transcriptional Expression of Repair Genes Are Differentially Regulated By 5-HT1F Receptor Agonism

Session Information

  • AKI: Mechanisms - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Victor Santiago Raj, Paul, The University of Arizona College of Pharmacy, Tucson, Arizona, United States
  • Hurtado, Kevin A., The University of Arizona College of Pharmacy, Tucson, Arizona, United States
  • Janda, Jaroslav, The University of Arizona College of Pharmacy, Tucson, Arizona, United States
  • Schnellmann, Rick G., The University of Arizona College of Pharmacy, Tucson, Arizona, United States

Acute kidney injury (AKI) is often accompanied by a persistent reduction in mitochondrial function, fatty acid oxidation and vascular injury. We have shown that the FDA-approved 5-HT1F receptor agonist lasmiditan stimulates mitochondrial biogenesis (MB), decreases vascular injury, and accelerates renal recovery in a mouse model of AKI. Given recent studies reporting conserved cellular responses and profiling successful and failed repair genes following AKI, we sought to explore the role of lasmiditan on these repair genes.


Male 8-week-old C57B/6J mice were administered 0.3 mg/kg lasmiditan or vehicle daily beginning 24h after ischemia/reperfusion-induced AKI (I/R-AKI) and continuing for 144h (n=6/group). The kidneys were collected and gene and protein expression of select repair genes analyzed in renal cortices.


Serum creatinine and kidney injury marker 1 (KIM1) were maximally elevated 24h after IR-AKI. Lasmiditan treatment decreased serum creatinine and KIM1 compared to vehicle by 144h after I/R-AKI. qRT-PCR analysis 24h following I/R-AKI revealed decreased expression of successful repair genes ACSM2a, LRP2, SLC5A12 and HNF4A, and increased expression of failed repair genes VCAM1, LCN2, RELB and KCNIP4 in the renal cortex of injured mice. Lasmiditan treatment increased successful repair gene expression compared to vehicle treatment by 144h after I/R-AKI; but had no effect on failed repair genes. These findings were confirmed using immunoblot analysis.


While these data support lasmiditan-induced regulation of successful repair genes following I/R-AKI, contributing to increased fatty acid metabolism, reabsorption of lactate, and decreased inflammation, the mechanism remains unclear. Continued use of this approach will allow us to identify and assess key genes responsible for pathophysiological changes during AKI, other renal pathologies, and the effects of drugs stimulating repair/recovery.


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