Suppression of SOCS3 expression in macrophage cells: Potential application in diabetic wound healing.
Int J Biol Macromol
; 262(Pt 1): 129876, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38310055
ABSTRACT
Impaired polarization of M1 to M2 macrophages has been reported in diabetic wounds. We aimed to improve this polarization by down-regulation of expression of the "Suppressor of Cytokine Signaling 3" (SOCS3) gene in macrophages. Two oligodeoxynucleotide (ASO) sequences were designed against SOC3 mRNA and were loaded to mannosylated-polyethyleneimine (Man-PEI). The optimum N/P ratio for Man-PEI-ASO was determined to be 8 based on loading efficiency, particle size, zeta potential, cellular uptake and cytotoxicity assay. pH stability of ASO in Man-PEI-ASO and its protection from DNase I was confirmed. After in vitro treatment of macrophages with Man-PEI-ASO, SOCS3 was downregulated, SOCS1 upregulated, and SOCS1/SOCS3 ratio increased. Also, expressions of macrophage markers of M2 (IL-10, Arg1, CD206) increased and those of M1 (IL-1ß, NOS2, CD68) decreased, and secretion of pro-inflammatory cytokines (TNF-α and IL-1ß) decreased while that of anti-inflammatory cytokine IL-4 increased. All suggested a polarization into M2 phenotype. Finally, the Man-PEI-ASO was loaded in hydrogel and applied to a diabetic wound model in mice. It improved the healing to the level observed in non-diabetic wounds. We show that using antisense sequences against SOC3 mRNA, macrophage polarization could be directed into the M2 phenotype and healing of diabetic wound could be highly improved.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Diabetes Mellitus
/
Proteínas Supressoras da Sinalização de Citocina
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Macrófagos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Biol Macromol
/
Int. j. biol. macromol
/
International journal of biological macromolecules
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Irã
País de publicação:
Holanda