Molecular profiling of NOD mouse islets reveals a novel regulator of insulitis onset.
Sci Rep
; 14(1): 14669, 2024 06 25.
Article
em En
| MEDLINE
| ID: mdl-38918575
ABSTRACT
Non-obese diabetes (NOD) mice are an established, spontaneous model of type 1 diabetes in which diabetes develops through insulitis. Using next-generation sequencing, coupled with pathway analysis, the molecular fingerprint of early insulitis was mapped in a cohort of mice ranging from 4 to 12 weeks of age. The resulting dynamic timeline revealed an initial decrease in proliferative capacity followed by the emergence of an inflammatory signature between 6 and 8 weeks that increased to a regulatory plateau between 10 and 12 weeks. The inflammatory signature is identified by the activation of central immunogenic factors such as Infg, Il1b, and Tnfa, and activation of canonical inflammatory signaling. Analysis of the regulatory landscape revealed the transcription factor Atf3 as a potential novel modulator of inflammatory signaling in the NOD islets. Furthermore, the Hedgehog signaling pathway correlated with Atf3 regulation, suggesting that the two play a role in regulating islet inflammation; however, further studies are needed to establish the nature of this connection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Ilhotas Pancreáticas
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Camundongos Endogâmicos NOD
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Diabetes Mellitus Tipo 1
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Fator 3 Ativador da Transcrição
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article