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

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 fa...

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Veröffentlicht in:	Nature communications Jg. 10; H. 1; S. 3303 - 17
Hauptverfasser:	Lazareth, Hélène, Henique, Carole, Lenoir, Olivia, Puelles, Victor G., Flamant, Martin, Bollée, Guillaume, Fligny, Cécile, Camus, Marine, Guyonnet, Lea, Millien, Corinne, Gaillard, François, Chipont, Anna, Robin, Blaise, Fabrega, Sylvie, Dhaun, Neeraj, Camerer, Eric, Kretz, Oliver, Grahammer, Florian, Braun, Fabian, Huber, Tobias B., Nochy, Dominique, Mandet, Chantal, Bruneval, Patrick, Mesnard, Laurent, Thervet, Eric, Karras, Alexandre, Le Naour, François, Rubinstein, Eric, Boucheix, Claude, Alexandrou, Antigoni, Moeller, Marcus J., Bouzigues, Cédric, Tharaux, Pierre-Louis
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 24.07.2019 Nature Publishing Group Nature Portfolio
Schlagworte:	45 45/77 45/91 631/80/304 631/80/84 64/60 692/4022/1585/2759/1523 82/1 82/29 82/51 82/80 96 Animal models Animals Biopsy Capillaries CD44 antigen CD9 antigen Cell Behavior Cell Movement - genetics Cell proliferation Cell Proliferation - genetics Cellular Biology Damage prevention Disease Disease control Disease Progression Epidermal growth factor Epithelial cells Female Gene targeting Genotype & phenotype Glomerulonephritis Glomerulonephritis - genetics Glomerulonephritis - metabolism Glomerulonephritis - pathology Glomerulosclerosis, Focal Segmental - genetics Glomerulosclerosis, Focal Segmental - metabolism Glomerulosclerosis, Focal Segmental - pathology Hospitals Human health and pathology Humanities and Social Sciences Humans Kidney Diseases - metabolism Kidney Diseases - pathology Kidneys Lesions Life Sciences Male Medicine Mice Mice, Inbred C57BL multidisciplinary Nephrology Phenotypes Renal failure Science Science (multidisciplinary) Subcellular Processes Tetraspanin 29 - genetics Tetraspanin 29 - metabolism Tetraspanin 29 - physiology Urology and Nephrology
ISSN:	2041-1723, 2041-1723
Online-Zugang:	Volltext
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Zusammenfassung:	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. In both focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN), kidney injury is characterised by the invasion of glomerular tufts by parietal epithelial cells (PECs). Here Lazareth et al. identify the tetraspanin CD9 as a key regulator of PEC migration, and find its upregulation in FSGS and CGN contributes to kidney injury in both diseases.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC6656772
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-11013-2