Delivery of Synthetic Interleukin-22 mRNA to Hepatocytes via Lipid Nanoparticles Alleviates Liver Injury.
Small
; : e2401499, 2024 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-39082407
ABSTRACT
Hepatocellular injury, a pivotal contributor to liver diseases, particularly hepatitis, lacks effective pharmacological treatments. Interleukin-22 (IL-22), crucial for liver cell survival, shows potential in treating liver diseases by regulating repair and regeneration through signal transducer and activator of transcription 3 (STAT3) activation. However, the short half-life and off-target effects limit its clinical applications. To address these issues, lipid nanoparticles are employed to deliver synthetic IL-22 mRNA (IL-22/NP) for in situ IL-22 expression in hepatocytes. The study reveals that IL-22/NP exhibits liver-targeted IL-22 expression, with increased IL-22 levels detected in the liver as early as 3 h postintravenous injection, lasting up to 96 h. Furthermore, IL-22/NP activates STAT3 signaling in an autocrine or paracrine manner to upregulate downstream factors Bcl-xL and CyclinD1, inhibiting hepatocyte apoptosis and promoting cell proliferation. The therapeutic efficacy of IL-22/NP is demonstrated in both chronic and acute liver injury models, suggesting IL-22 mRNA delivery as a promising treatment strategy for hepatitis and liver diseases involving hepatocellular injury.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article