The miR-15b-5p/miR-379-3p-FOXO axis regulates cell cycle and apoptosis in scleral remodeling during experimental myopia.
J Transl Med
; 22(1): 710, 2024 Jul 30.
Article
em En
| MEDLINE
| ID: mdl-39080755
ABSTRACT
BACKGROUND:
Myopia is one of the most common eye diseases in children and adolescents worldwide, and scleral remodeling plays a role in myopia progression. However, the identity of the initiating factors and signaling pathways that induce myopia-associated scleral remodeling is still unclear. This study aimed to identify biomarkers of scleral remodeling to elucidate the pathogenesis of myopia.METHODS:
The gene expression omnibus (GEO) and comparative toxicogenomics database (CTD) mining were used to identify the miRNA-mRNA regulatory network related to scleral remodeling in myopia. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence, H&E staining, Masson staining, and flow cytometry were used to detect the changes in the FOXO signaling pathway, fibrosis, apoptosis, cell cycle, and other related factors in scleral remodeling.RESULTS:
miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. Confirmatory studies confirmed that the axial length of the eye was significantly increased, the scleral thickness was thinner, the levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased, and the levels of IGF1R were decreased in Len-induced myopia (LIM) group. CDK2, cyclin D1 (CCND1), and cell cycle block assessed by flow cytometry indicated G1/S cell cycle arrest in myopic sclera. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addition, we found that the levels of transforming growth factor-ß1 (TGF-ß1), collagen type 1 (COL-1), and α-smooth muscle actin (α-SMA) were decreased, suggesting scleral remodeling occurred in myopia.CONCLUSIONS:
miR-15b-5p/miR-379-3p can regulate the scleral cell cycle and apoptosis through the IGF1R/PTEN/FOXO signaling pathway, thereby promoting scleral remodeling in myopia progression.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclera
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Transdução de Sinais
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Ciclo Celular
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Apoptose
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MicroRNAs
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Fatores de Transcrição Forkhead
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Miopia
Limite:
Animals
Idioma:
En
Revista:
J Transl Med
Ano de publicação:
2024
Tipo de documento:
Article