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Crescents derive from single podocyte progenitors and a drug enhancing their differentiation attenuates crescentic glomerulonephritis* (Record no. 870)

MARC details
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Personal name Melica, Maria Elena
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9 (RLIN) 2055
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Title Crescents derive from single podocyte progenitors and a drug enhancing their differentiation attenuates crescentic glomerulonephritis*
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Date of publication, distribution, etc. 2022-08-10.
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General note /pmc/articles/PMC7614034/
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General note /pubmed/35947676
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Summary, etc. Crescentic glomerulonephritis is characterized by vascular necrosis and the formation of parietal epithelial cell (PEC) hyperplasia, but little is known about the molecular mechanisms driving this process. Inducing crescentic glomerulonephritis in several Pax2Cre reporter mouse lines revealed that crescents derive from clonal expansion of single immature PECs. Preemptive and delayed histone deacetylase inhibition with panobinostat, a drug used for the treatment of hematopoietic stem cell disorders, attenuated crescentic glomerulonephritis, and recovered kidney function. 3D confocal microscopy and STED super-resolution imaging of glomeruli showed that, in addition to exerting an anti-inflammatory and immunosuppressive effect, panobinostat turned the uncontrolled hyperplasia of a specific immature PEC subset into a controlled differentiation into podocytes thereby restoring the injured glomerular filtration barrier. Single cell RNA sequencing of human renal progenitor cultures identified an immature stratifin+ subset and expansion of a stratifin-expressing progenitor in human crescentic glomerulonephritis was associated with a poor outcome. Treatment of human PECs with panobinostat attenuated stratifin expression in podocyte progenitors, reduced their proliferation but promoted their differentiation into podocytes. These results offer mechanistic insights into the formation of glomerular crescents and demonstrate that selective targeting of progenitors can attenuate crescent formation and the deterioration of kidney function in crescentic glomerulonephritis.
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Language note en
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Personal name Antonelli, Giulia
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9 (RLIN) 2056
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Personal name Semeraro, Roberto
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9 (RLIN) 2057
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Personal name Angelotti, Maria Lucia
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9 (RLIN) 2058
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Personal name Lugli, Gianmarco
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9 (RLIN) 2059
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Personal name Landini, Samuela
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9 (RLIN) 2060
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Personal name Ravaglia, Fiammetta
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9 (RLIN) 2061
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Personal name La Regina, Gilda
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9 (RLIN) 2062
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Personal name Conte, Carolina
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9 (RLIN) 2063
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Personal name De Chiara, Letizia
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9 (RLIN) 2064
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Personal name Peired, Anna Julie
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9 (RLIN) 2065
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Personal name Mazzinghi, Benedetta
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9 (RLIN) 2066
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Personal name Donati, Marta
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9 (RLIN) 2067
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Personal name Molli, Alice
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9 (RLIN) 2068
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Personal name Steiger, Stefanie
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9 (RLIN) 2069
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Personal name Magi, Alberto
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9 (RLIN) 2070
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Personal name Bartalucci, Niccolò
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9 (RLIN) 2071
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Personal name Raglianti, Valentina
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9 (RLIN) 2072
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Personal name Guzzi, Francesco
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9 (RLIN) 2073
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Personal name Maggi, Laura
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9 (RLIN) 2074
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Personal name Annunziato, Francesco
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9 (RLIN) 2075
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Personal name Burger, Alexa
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9 (RLIN) 2076
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Personal name Lazzeri, Elena
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9 (RLIN) 2077
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Personal name Anders, Hans-Joachim
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9 (RLIN) 2078
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Personal name Lasagni, Laura
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9 (RLIN) 2079
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Personal name Romagnani, Paola
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9 (RLIN) 2080
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Note Sci Transl Med
856 41 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://dx.doi.org/10.1126/scitranslmed.abg3277">http://dx.doi.org/10.1126/scitranslmed.abg3277</a>
Public note Connect to this object online.

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