The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2019

The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

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Olivia Lenoir
Eric Camerer
Cedric Bouzigues
  • Function : Author
  • PersonId : 956065

Abstract

The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here we show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions.
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Dates and versions

inserm-02439082 , version 1 (14-01-2020)

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Hélène Lazareth, Carole Henique, Olivia Lenoir, Victor Puelles, Martin Flamant, et al.. The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression. Nature Communications, 2019, 10 (1), pp.3303. ⟨10.1038/s41467-019-11013-2⟩. ⟨inserm-02439082⟩
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