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Kidney Week

Abstract: TH-PO113

Proximal Tubule β2 Adrenergic Receptor Is Responsible for Formoterol-Induced Recovery of Mitochondrial and Renal Function After AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Cameron, Robert Bruce, Medical University of South Carolina, Charleston, South Carolina, United States
  • Gibbs, Whitney Sharee, Medical University of South Carolina, Charleston, South Carolina, United States
  • Dupre, Tess, University of Arizona College of Pharmacy, Tucson, Arizona, United States
  • Miller, Siennah R., University of Arizona College of Pharmacy, Tucson, Arizona, United States
  • Megyesi, Judit, University of Arkansas for Medical Science, Little Rock, Arkansas, United States
  • Schnellmann, Rick G., University of Arizona, Tucson, Arizona, United States

Numerous cell types play a role in the pathogenesis of AKI, including immune, endothelial, and renal proximal tubule cells. Our laboratory demonstrated that the β2 adrenergic receptor (β2AR) agonist formoterol stimulates mitochondrial biogenesis (MB) and accelerates the recovery of renal and mitochondrial function in mice following ischemia-reperfusion injury (IRI). However, the cell type(s) responsible for this recovery remains unknown.


ADRB2Flox/Flox (WT) mice were mated with γGT-Cre mice to generate γGT-Cre:ADRB2Flox/Flox (KO) mice with proximal tubule deletion of the β2AR. These mice were subjected to renal IRI and were treated once daily with formoterol or vehicle beginning at 24 h and euthanized at 144 h.


Compared to WT, KO mice had 80% lower renal cortical ADRB2 mRNA and DNA. At 24 h following IRI, WT and KO mice had a similar loss of renal function as measured by serum creatinine. At 144 h following IRI, both WT and KO mice treated with vehicle exhibited persistent renal dysfunction as measured by elevated serum creatinine (SCr), KIM-1 protein, and tubular necrosis. Following treatment with formoterol, WT mice, but not KO mice, exhibited accelerated recovery of renal function. Treatment with formoterol increased mitochondrial protein expression and mtDNA copy number in WT but not KO mice. Sham-operated KO mice also had fewer mitochondria than WT mice as assessed by transmission electron microscopy. Formoterol restored mitochondrial number and density in WT but not KO mice.


Following AKI, formoterol activates the β2AR and stimulates MB in proximal tubule cells to accelerate the recovery of renal function. The β2AR also regulates mitochondrial homeostasis in healthy proximal tubule cells. These data underscore the importance of the proximal tubule cell as a therapeutic target for AKI. Thus, targeting compounds that induce MB in renal proximal tubule cells may provide more effective treatments for AKI.


  • NIDDK Support