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Can J Physiol Pharmacol ; 99(12): 1288-1297, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34310900

RESUMEN

The effects of long non-coding RNAs (lncRNAs) on the proliferation of hypertrophic scars have been described, however, the underlying mechanisms are not well characterized. The present study aimed to investigate the mechanisms of lncRNA H19 in hypertrophic scars. The effects of the lncRNA H19 on the proliferation and apoptosis of hypertrophic scar fibroblasts (HSFs) were analyzed using 5'-ethynyl-2'-deoxyuridine staining, flow cytometry, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The results revealed H19 promoted the proliferation and inhibited the apoptosis in HSF. In addition, the binding associations between H19 and microRNA-194 (miR-194), and miR-194 and insulin-like growth factor I receptor (IGF1R) were identified using bioinformatics screening and verified using dual-luciferase assays. Furthermore, the effects of the IGF1R knockdown on H19-induced HSF phenotypes and regulation over the p38 MAPK pathway were determined. Mechanistically, miR-194 was identified as the downstream effector of the H19-mediated phenotypes of HSFs through its ability to directly target IGF1R, thus modulating the p38 MAPK signaling pathway. In conclusion, the findings suggested that H19 may inhibit the apoptosis and promote the proliferation of HSFs through the miR-194/IGF1R/p38 MAPK signaling axis, thereby contributing to the progression of hypertrophic scars. These findings may provide novel targets for the treatment of hypertrophic scars.


Asunto(s)
Apoptosis/genética , Proliferación Celular/genética , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/patología , Fibroblastos/patología , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/fisiología , Línea Celular , Humanos , Sistema de Señalización de MAP Quinasas , Receptor IGF Tipo 1 , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
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