Podocyte Density and Albuminuria in Aging Diabetic Ins2± Mice with or Without Adenosine A1 Receptor Signaling
Received 5 February 2019
Accepted for publication 27 November 2019
Published 21 February 2020 Volume 2020:13 Pages 19—26
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Professor Pravin Singhal
Robert Faulhaber-Walter, 1–3 Lanping Jiang, 4 Diane Mizel, 2 Patricia M Zerfas, 2 Jeffrey B Kopp, 2 Jurgen B Schnermann, 2 Limeng Chen, 2, 4 Mario Schiffer 3, 5
1Facharztzentrum Aarberg, Waldshut-Tiengen, Germany; 2NIDDK, National Institutes of Health, Bethesda, MD, USA; 3Department of Nephrology, Medical School Hannover, Hannover, Germany; 4Peking Union Medical College Hospital, Beijing, People’s Republic of China; 5Department of Nephrology, University of Erlangen, Erlangen, Germany
Correspondence: Robert Faulhaber-Walter
Facharztzentrum Aarberg, Tannenstrasse 4, Waldshut-Tiengen 79761, Germany
Aim of Study: To investigate podocyte density in aging diabetic Ins2± and Ins2±, A1AR-/- mouse models in C57Bl/6 background.
Methods: Ins2± mice and especially Ins2±, adenosine A1 receptor knockout mice (Ins2±, A1AR-/-) are mouse models with a phenotype of diabetic nephropathy. Aged mice (at ∼ 40 weeks) were assessed for glomerular filtration barrier function by measuring albuminuria, glomerular filtration, glomerular damage by electron microscopy, and podocyte numbers by Wilms Tumor protein (WT-1) staining.
Results: Compared to healthy wild-type mice, both diabetic mouse models developed diabetic nephropathy, including hyperfiltration (p< 0.01) and albuminuria (p< 0.05). Typical diabetic structural glomerular and podocyte damage was visualized by electron microscopy. Podocyte count per glomerular area (podocyte density) was significantly decreased in both diabetic mouse models (p< 0.01). In contrast, no significant correlation was detected between albuminuria and absolute podocyte count per glomerulus.
Conclusion: The amount of albuminuria as marker of diabetic nephropathy does not correlate with the podocytes density; however, a relative podocyte deficiency became evident with an increase in glomerular area in the diabetic animals, suggesting a relative podocytopenia.
Keywords: diabetes nephropathy podocyte mouse Akita WT-1
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