Activating transcription factor 3 inhibits angiotensin IIinduced cardiomyocyte viability and fibrosis by activating the transcription of cysteinerich angiogenic protein 61.
Mol Med Rep
; 26(5)2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-36102309
ABSTRACT
Depletion of activating transcription factor 3 (ATF3) expression has previously been reported to promote hypertrophy, dysfunction and fibrosis in stress overloadinduced hearts; however, the mechanism involved remains poorly understood. In the present study, the mechanism underlying the activation of cysteinerich angiogenic protein 61 (Cyr61) by ATF3 in hyperproliferative and fibrotic human cardiac fibroblasts (HCFs), induced by angiotensin II (Ang II), was evaluated. The mRNA and protein expression levels of ATF3 and Cyr61 were assessed using reverse transcriptionquantitative PCR and western blotting, respectively. The Cell Counting Kit8 assay was used to assess cell viability. Cell migration was assessed using the wound healing assay and western blotting, whereas the extent of cell fibrosis was evaluated using immunofluorescence staining and western blotting. The binding site of ATF3 to the Cyr61 promoter was predicted using the JASPAR database, and verified using luciferase reporter and chromatin immunoprecipitation assays. The results demonstrated that the mRNA and protein expression levels of ATF3 were significantly upregulated in Ang IIinduced HCFs. Overexpression of ATF3 significantly inhibited the Ang IIinduced viability, migration and fibrosis of HCFs, whereas ATF3 knockdown mediated significant opposing effects. Mechanistically, ATF3 was demonstrated to transcriptionally activate Cyr61. Cyr61 silencing was subsequently revealed to reverse the effects of ATF3 overexpression on HCFs potentially via regulation of the TGFß/Smad signaling pathway. The results of the present study suggested that ATF3 could suppress HCF viability and fibrosis via the TGFß/Smad signaling pathway by activating the transcription of Cyr61.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
/
Fator 3 Ativador da Transcrição
/
Proteína Rica em Cisteína 61
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article