Targeted degradation of hexokinase 2 for antiinflammatory treatment in acute lung injury.
Mol Med Rep
; 29(5)2024 05.
Article
em En
| MEDLINE
| ID: mdl-38516767
ABSTRACT
Acute lung injury (ALI) is an acute inflammatory lung disease associated with both innate and adaptive immune responses. Hexokinase 2 (HK2) is specifically highly expressed in numerous types of inflammationrelated diseases and models. In the present study in vitro and in vivo effects of targeted degradation of HK2 on ALI were explored. The degradation of HK2 by the targeting peptide TAT (transactivator of transcription protein of HIV1)ataxin 1 (ATXN1)chaperonemediated autophagytargeting motif (CTM) was demonstrated by ELISA and western blotting in vitro and in vivo. The inhibitory effects of TATATXN1CTM on lipopolysaccharide (LPS)induced inflammatory responses were examined using ELISAs. The therapeutic effects of TATATXN1CTM on LPSinduced ALI were examined via histological examination and ELISAs in mice. 10 µM TATATXN1CTM administration decreased HK2 protein expression and the secretion of proinflammatory cytokines (TNFα and IL1ß) without altering HK2 mRNA expression in LPStreated both in vitro and in vivo, while pathological lung tissue damage and the accumulation of leukocytes, neutrophils, macrophages and lymphocytes in ALI were also significantly suppressed by 10 µM TATATXN1CTM treatment. TATATXN1CTM exhibited antiinflammatory activity in vitro and decreased the severity of ALI in vivo. HK2 degradation may represent a novel therapeutic approach for ALI.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesão Pulmonar Aguda
/
Hexoquinase
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article