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The β 2 ‐Adrenergic Receptor Agonist Formoterol Decreases Fibrotic And Mitochondrial Fusion/Fission Proteins in a Mouse Model of Diabetic Nephropathy
Author(s) -
Cleveland Kristan,
Cameron Robert B,
Brosius Frank C,
Schnellmann Rick G
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.514.14
Subject(s) - endocrinology , mfn2 , medicine , formoterol , diabetic nephropathy , mitochondrial fission , mfn1 , mitochondrial biogenesis , mitochondrial fusion , kidney , diabetes mellitus , irbesartan , creatinine , mitochondrion , biology , blood pressure , biochemistry , budesonide , microbiology and biotechnology , corticosteroid , mitochondrial dna , gene
Diabetic nephropathy (DN) is a 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 β 2 ‐adrenergic receptor agonist previously shown to induce mitochondrial biogenesis (MB) and promote recovery from acute kidney injury, on fibrotic and mitochondrial proteins in db/db mice, an established mouse model for studying type 2 diabetic nephropathy (T2DN). Female diabetic db/db and non‐diabetic db/m (control) mice 9 weeks of age were treated with formoterol or saline daily for three weeks. Body weight was measured weekly and renal function was measured using serum creatinine levels. Kidneys were harvested and changes in expression of mitochondrial and fibrotic proteins were measured using immunoblot analysis. At 12 weeks of age, serum creatinine increased slightly in diabetic mice and decreased in formoterol‐treated diabetic mice without altering body weight. The mitochondrial fission protein phospho‐Drp1, and profibrotic 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 the kidneys of diabetic mice and increased to control levels with formoterol treatment. Formoterol treatment in a T2DN model decreased kidney profibrotic proteins and restored mitochondrial fusion/fission protein levels. These results suggest that formoterol could be a potential therapy for DN. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .