1. Immune Reactive Ezrin Surface Area Increases in Glomerular Podocytes of STZ Diabetic Rats Precede Their Detachment, Is Prevented by Phlorizin But Not by Insulin
- Author
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Gavin I. Welsh, Musleeha Chesor, Mario Barac-Nieto, Issam M. Francis, Slava Malatiali, and Moin A. Saleem
- Subjects
Basement membrane ,medicine.medical_specialty ,urogenital system ,Phlorizin ,Insulin ,medicine.medical_treatment ,General Medicine ,Glomerular Hypertrophy ,Glomerulus (kidney) ,urologic and male genital diseases ,female genital diseases and pregnancy complications ,Podocyte ,Muscle hypertrophy ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,Ezrin ,chemistry ,Internal medicine ,medicine - Abstract
Glomerular tuft immune reactive Ezrin surface area (EzA) and fraction of EzA to total glomerular tuft area significantly increased, indicating podocyte growth, rounding and altered cytoskeletal interactions at 1 week of STZ diabetes. Podocyte number per glomerulus (WT1+ nuclei) did not change indicating no detachment, but density decreased due to tuft hypertrophy. Treatment with PLZ or Insulin for one week, prevented increase in proteinuria and hyperglycemia but not the decrease in podocyte density. PLZ but not Insulin prevented increase in ezrin positive area in glomeruli and per podocyte. In podocytes in culture neither 25 mM glucose with or without PLZ (2.5 or 25 uM) altered Ezrin expression measured in western blots. In summary, the Ezrin positive glomerular surface area increase seen after 1 week of STZ diabetes, reflects altered podocyte morphology and cytoskeletal interactions, prevented by PLZ but not by insulin. Ezrin area increase preceded podocyte detachment and in podocytes in culture is not associated with increases in podocyte Ezrin protein expression. It is a likely precursor of shape changes in podocytes and of alterd interactions with basement membrane that contribute to detachment and thickening. Glomerular capillary tuft hypertrophy and reduced podocyte density persisted despite PLZ or insulin treatments, independently of levels of glycemia and of proteinuria.
- Published
- 2020
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