Transcriptomic profiling of sciatic nerves and dorsal root ganglia reveals site-specific effects of prediabetic neuropathy.
Transl Res
; 270: 24-41, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38556110
ABSTRACT
Peripheral neuropathy (PN) is a severe and frequent complication of obesity, prediabetes, and type 2 diabetes characterized by progressive distal-to-proximal peripheral nerve degeneration. However, a comprehensive understanding of the mechanisms underlying PN, and whether these mechanisms change during PN progression, is currently lacking. Here, gene expression data were obtained from distal (sciatic nerve; SCN) and proximal (dorsal root ganglia; DRG) injury sites of a high-fat diet (HFD)-induced mouse model of obesity/prediabetes at early and late disease stages. Self-organizing map and differentially expressed gene analyses followed by pathway enrichment analysis identified genes and pathways altered across disease stage and injury site. Pathways related to immune response, inflammation, and glucose and lipid metabolism were consistently dysregulated with HFD-induced PN, irrespective of injury site. However, regulation of oxidative stress was unique to the SCN while dysregulated Hippo and Notch signaling were only observed in the DRG. The role of the immune system and inflammation in disease progression was supported by an increase in the percentage of immune cells in the SCN with PN progression. Finally, when comparing these data to transcriptomic signatures from human patients with PN, we observed conserved pathways related to metabolic dysregulation across species, highlighting the translational relevance of our mouse data. Our findings demonstrate that PN is associated with distinct site-specific molecular re-programming in the peripheral nervous system, identifying novel, clinically relevant therapeutic targets.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estado Pré-Diabético
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Nervo Isquiático
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Perfilação da Expressão Gênica
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Gânglios Espinais
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Camundongos Endogâmicos C57BL
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Transl Res
Assunto da revista:
MEDICINA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos