The 5-hydroxytryptamine receptor 1F stimulates mitochondrial biogenesis and angiogenesis in endothelial cells

Tess V. Dupre, Dorea P. Jenkins, Robin C. Muise-Helmericks, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

A hallmark of acute kidney injury (AKI) is vascular rarefication and mitochondrial dysfunction. Promoting vascular recovery following AKI could facilitate kidney repair as the vasculature is responsible for oxygen and nutrient delivery to extravascular tissues. Little is known about mitochondrial biogenesis (MB) in endothelial cells, and the role of 5-HT1F receptor signaling in MB has only been studied in epithelial cells. Our laboratory has shown that stimulating MB through the 5-HT1F receptor promotes recovery from AKI and that 5-HT1F receptor knockout mice have decreased MB and poor renal recovery. We hypothesized that the 5-HT1F receptor plays a role in vascular homeostasis and mediates MB in renal endothelial cells. 5-HT1F receptor knockout mice had decreased renal vascular content, as evidenced by decreased CD31+ endothelial cells and αSMA+ vessels. Human glomerular endothelial cells (HEC) and mouse glomerular endothelial cells (MEC) expressed the 5-HT1F receptor. Treatment of HEC and MEC with 5-HT1F receptor agonists LY344864 or lasmiditan (0–500 nM) induced MB as evidenced by maximal mitochondrial respiration, a marker of MB. HEC and MEC treated with lasmiditan or LY344864 also had increased nuclear- and mitochondrial-encoded proteins (PGC1α, COX-1, and VDAC), and mitochondrial number, confirming MB. Treatment of HEC with LY344864 or lasmiditan enhanced endothelial branching morphogenesis and migration, indicating a role for 5-HT1F receptor stimulation in angiogenic pathways. We propose that stimulation of 5-HT1F receptor is involved in MB in endothelial cells and that treatment with 5-HT1F receptor agonists could restore stimulate repair and recovery following kidney injury.

Original languageEnglish (US)
Article number113644
JournalBiochemical Pharmacology
Volume169
DOIs
StatePublished - Nov 2019

Keywords

  • Angiogenesis
  • Endothelial cells
  • Mitochondrial biogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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