Crescents derive from single podocyte progenitors and a drug enhancing their differentiation attenuates crescentic glomerulonephritis* (Record no. 1833)
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042 ## - AUTHENTICATION CODE | |
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Authentication code | dc |
100 10 - MAIN ENTRY--PERSONAL NAME | |
Personal name | Melica, Maria Elena |
Relator term | author |
9 (RLIN) | 2055 |
245 00 - TITLE STATEMENT | |
Title | Crescents derive from single podocyte progenitors and a drug enhancing their differentiation attenuates crescentic glomerulonephritis* |
260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
Date of publication, distribution, etc. | 2022-08-10. |
500 ## - GENERAL NOTE | |
General note | /pmc/articles/PMC7614034/ |
500 ## - GENERAL NOTE | |
General note | /pubmed/35947676 |
520 ## - SUMMARY, ETC. | |
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. |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | |
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Language note | en |
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Topical term or geographic name as entry element | Article |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
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Personal name | Antonelli, Giulia |
Relator term | author |
9 (RLIN) | 2056 |
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Personal name | Semeraro, Roberto |
Relator term | author |
9 (RLIN) | 2057 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Angelotti, Maria Lucia |
Relator term | author |
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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700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Conte, Carolina |
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9 (RLIN) | 2063 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
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 |
Relator term | author |
9 (RLIN) | 2070 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Bartalucci, Niccolò |
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9 (RLIN) | 2071 |
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Personal name | Raglianti, Valentina |
Relator term | author |
9 (RLIN) | 2072 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Guzzi, Francesco |
Relator term | author |
9 (RLIN) | 2073 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Maggi, Laura |
Relator term | author |
9 (RLIN) | 2074 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Annunziato, Francesco |
Relator term | author |
9 (RLIN) | 2075 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Burger, Alexa |
Relator term | author |
9 (RLIN) | 2076 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Lazzeri, Elena |
Relator term | author |
9 (RLIN) | 2077 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Anders, Hans-Joachim |
Relator term | author |
9 (RLIN) | 2078 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Lasagni, Laura |
Relator term | author |
9 (RLIN) | 2079 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Romagnani, Paola |
Relator term | author |
9 (RLIN) | 2080 |
786 0# - DATA SOURCE ENTRY | |
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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