Association between MeCP2 and Smad7 in the pathogenesis and development of pathological scars.
J Plast Surg Hand Surg
; 55(5): 284-293, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-33475023
ABSTRACT
To explore the relationship between methylated binding protein 2 (MeCP2) and mothers against decapentaplegic homolog 7 (Smad7) in the pathogenesis and development of pathological scars. Immunohistochemistry, Western blot and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of MeCP2 in different types of human scars and hypertrophic scars at different growth times. The methylation status of Smad7 gene promoter in different scar tissues was determined by methylation-specific PCR. After transfection with MeCP2-siRNA (small interfering RNA) in human keloid fibroblasts, MTT assay was used to assess the proliferation activity of keloid fibroblasts, while RT-PCR and Western blot assays were used to detect the expression levels of MeCP2, transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), phospho-Smad2 (p-Smad2) and Smad7. MeCP2 was mainly expressed in the nucleus of fibroblasts. The mRNA and protein levels of MeCP2 were significantly higher in keloids than in hypertrophic scars, normal scars and normal skin (p<.05). The expression level of MeCP2 in hypertrophic scars during the growth period of <6 months was markedly higher than that of >6 months (p<.05). The methylation level of Smad7 was significantly higher in keloids compared to normal skin. After MeCP2 silencing, the proliferation rate of human keloid fibroblasts was decreased, the mRNA and protein levels of Smad7 were increased, and the expression levels of TGF-ß1, α-SMA and p-Smad2 were decreased (p<.05). MeCP2 and Smad7 play an important role in formation of pathological scars. During keloid formation, MeCP2 weakens the inhibitory effect of Smad7 on p-Smad2/3 by downregulating the expression of Smad7, which in turn promotes fibrosis and scar hyperplasia.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cicatriz Hipertrófica
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Proteína Smad7
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Proteína 2 de Ligação a Metil-CpG
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Queloide
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Plast Surg Hand Surg
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China