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Role of the mineralocorticoi receptor in parietal epithelial cells activation

ABSTRACT: Focal segmental glomerulosclerosis (FSGS) is a common histological lesion in adults worldwide. It is caused by initial podocyte injury followed by a maladaptive activation of the glomerular parietal epithelial cells (PECs) and conduct to progressive scarring of glomeruli. Current knowledge of the pathophysiological mechanisms leading to PECs actvation is limited. Recent evidence indicates an active, destructive role for PECs in extracapillary glomerular diseases. This suggests that targeting such maladaptive responses could represent a novel therapeutic option to prevent kidney failure in patients. Yet, druggable pathways to prevent or stop PEC pathogenic behavior are still elusive. Here, we examined the role of the mineralocorticoid receptor (MR) signaling in PECs. We demonstrate that MR gene targeting specifically in PECs prevents PEC migration and proliferation after DOCA-salt administration and uninephrectomy in mice, a robust model of maladaptive FSGS. Remarkably, both MR deficiency in PECs ad MR pharmacological blockade using eplerenone were also efficient in preventing extracapillary lesions and glomerular failure in nephrotoxic serum-induced crescentic glomerulonephritis. Finally, we revealed a noteworthy overlap between pathways triggered by HB-EGF/EGFR signaling and aldosterone/MR signaling in PECs. Together, our results highlight the role of MR signaling in the pathophysiology of extracepillary glomerulopathies, FSGS, and crescentic glomerulonephritis, supporting MR antagonists as potential complementary therapeutic agents with original mode of action for such diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE282359 | GEO | 2025/10/19

REPOSITORIES: GEO

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