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


The Latest on Twitter

Kidney Week

Abstract: SA-PO606

5-HT1F Receptor Mediates Renal Vascular Homeostasis and Mitochondrial Biogenesis

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Dupre, Tess, University of Arizona, Tucson, Arizona, United States
  • Schnellmann, Rick G., University of Arizona, Tucson, Arizona, United States

Acute kidney injury (AKI) is a devastating disease with no treatment options. After AKI, there is a marked reduction in renal vasculature. Thus, promoting vascular recovery following AKI could facilitate renal repair as the vasculature is responsible for carrying oxygen and nutrients to extravascular tissues. Our laboratory has shown that stimulating mitochondrial biogenesis (MB) through the 5-HT1F receptor stimulates recovery from AKI. In contrast, 5HT1F receptor knockout mice have decreased MB and poor renal recovery. Importantly, induction of MB has been linked to increased angiogenesis. Thus, we hypothesized that the 5HT1F receptor plays a role in vascular homeostasis and mediates MB in renal endothelial cells.


Primary human glomerular endothelial cells (HEC) and mouse glomerular endothelial cells (MEC) were treated with the 5-HT1F receptor agonists LY344864 or lasmiditan (0-500 nM) for 24 or 72h. Mitochondrial respiration using Seahorse analysis, mitochondrial proteins using immunoblot analysis and mitochondrial copy number using qPCR analysis was determined. Immunohistochemical analysis for CD31 was performed on paraffin embedded kidney sections.


We determined that HEC and MEC express the 5-HT1F receptor. Treatment of HEC and MEC with LY344864 or lasmiditan induced MB, as evidenced by maximal mitochondrial respiration, a marker of MB. HEC that were treated with lasmiditan or LY344864 had increased expression of nuclear- and mitochondrial-encoded proteins (PGC1α, TFAM, NDUFS1, COX-1, and VDAC) and mitochondrial DNA copy number, confirming MB and increased mitochondrial content. Lastly, 5-HT1F receptor knockout mice had decreased renal vascular content, as immunohistochemical analysis revealed decreased CD31+ renal endothelial cells.


Stimulation of 5-HT1F receptor with LY344864 and lasmiditan induces MB in HEC and MEC, in vitro, and 5-HT1F receptor mediates vascular homeostasis, in vivo. We propose that inducing MB in endothelial cells after AKI could restore vascular function and stimulate renal repair and recovery.


  • Other NIH Support