Kidney Week

Abstract: SA-PO126

The β2-Adrenergic Receptor Agonist Formoterol Improves Renal Function and Decreases Fibrotic and Mitochondrial Fusion/Fission Proteins in a Mouse Model of Diabetic Nephropathy

Session Information

• Diabetic Kidney Disease: Basic - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Cleveland, Kristan H., University of Arizona, Tucson, Arizona, United States

Kristan H. Cleveland,

• Cameron, Robert Bruce, University of Arizona, Tucson, Arizona, United States

Robert Bruce Cameron,

• Brosius, Frank C., University of Arizona, Tucson, Arizona, United States

Frank C. Brosius,

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

Rick G. Schnellmann,

Background

Diabetic nephropathy (DN) is a significant cause of chronic kidney disease and accounts for 50% of all end-stage renal disease. Current therapies for DN, such as glycemic and blood pressure control and renin-angiotensin system blockade, only slow the progression of DN. Therefore, we examined the effect of formoterol, a β₂-adrenergic receptor agonist previously shown to induce mitochondrial biogenesis and promote recovery from acute kidney injury, on renal function and fibrotic and mitochondrial proteins in db/db mice, a validated mouse model of DN.

Methods

Female diabetic db/db and non-diabetic db/m (control) mice 9 weeks of age were treated with formoterol (0.3 mg/kg, i.p.) or saline daily for three weeks. Mice were placed in metabolic cages weekly for 18 hr and urine collected. Body weight and serum glucose were measured weekly and renal function was measured by serum creatinine levels. Kidneys were harvested after three weeks and changes in expression of mitochondrial and fibrotic proteins were measured using immunoblot analysis.

Results

At 12 weeks of age, formoterol decreased serum glucose and creatinine in diabetic mice compared to vehicle treated mice without altering body weight. Mitochondrial fission protein phospho-Drp1, and fibrotic proteins TGF-β1, phospho-SMAD3 and α-SMA were increased in diabetic mouse kidneys and were restored to control levels with formoterol treatment. Additionally, mitochondrial fusion proteins Mfn1 and Mfn2 were decreased in diabetic mouse kidneys and increased to control levels with formoterol treatment. Complete DN phenotyping is ongoing.

Conclusion

Formoterol treatment in a DN model resulted in improved serum creatinine, decreased kidney profibrotic protein levels and restored mitochondrial fusion/fission protein levels in a DN model. These results suggest that formoterol could be a potential therapy for DN.