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Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P + cells and pericyte coverage. Analysis of the mechanisms involved revealed the induction of bone morphogenetic protein-7 (BMP7) expression, a critical regulator of angiogenesis and kidney homeostasis, through a PDE5i-dependent downregulation of miR-22. In conclusion PDE5i slows the progression of DN in mice, improving hemodynamic parameters and vessel integrity. Regulation of miR-22/BMP7, an unknown mechanism of PDE5is in nephrovascular protection, might represent a novel therapeutic option for treatment of diabetic complications.

Original publication

DOI

10.1038/srep44584

Type

Journal article

Journal

Scientific reports

Publication Date

15/03/2017

Volume

7

Addresses

Department of Experimental Medicine, Sapienza University of Rome, Italy.

Keywords

Kidney, Animals, Humans, Mice, Diabetic Nephropathies, Kidney Failure, Chronic, Hypertension, Creatinine, Albumins, MicroRNAs, Glomerular Filtration Rate, Gene Expression Regulation, Male, Hemodynamics, Cyclic Nucleotide Phosphodiesterases, Type 5, Receptors, Urokinase Plasminogen Activator, Bone Morphogenetic Protein 7, Phosphodiesterase 5 Inhibitors, Biomarkers