Daniel Ackermann, Bruno Vogt, Murielle Bochud, Michel Burnier, Pierre-Yves Martin, Fred Paccaud, Georg Ehret, Idris Guessous, Belen Ponte, Menno Pruijm, Antoinette Pechère-Bertschi, Heidi Jamin, Rahel Klossner, Bernhard Dick, Markus G Mohaupt, Carine Gennari-Moser
AIMS: Glomerular damage indicated by proteinuria is a main symptom in diabetic nephropathy. Mineralocorticoid receptor (MR) antagonists (MRAs) are beneficial irrespective of aldosterone availability. Thus, we hypothesized an alternatively activated MR to promote glomerular damage in proteinuric diabetic nephropathy. Specifically, we aimed first to demonstrate the presence of steroid hormones serving as alternative MR targets in type II diabetic patients with proteinuric kidney disease, second whether MR selectivity was modified, third to characterize MR and glucocorticoid receptor (GR) expression and activity in glomerular cell types exposed to eu- and hyperglycemic conditions, fourth to characterize the pro-fibrotic potential of primary human renal mesangial cells (HRMC) upon stimulation with aldosterone and cortisol, and fifth to specify the involvement of the MR and/or GR in pro-fibrotic signaling...
2022: PloS One