miR-222 inhibits cardiac fibrosis in diabetic mice heart via regulating Wnt/ß-catenin-mediated endothelium to mesenchymal transition.
J Cell Physiol
; 235(3): 2149-2160, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31389030
ABSTRACT
miR-222 participates in many cardiovascular diseases, but its effect on cardiac remodeling induced by diabetes is unclear. This study evaluated the functional role of miR-222 in cardiac fibrosis in diabetic mice. Streptozotocin (STZ) was used to establish a type 1 diabetic mouse model. After 10 weeks of STZ injection, mice were intravenously injected with Ad-miR-222 to induce the overexpression of miR-222. miR-222 overexpression reduced cardiac fibrosis and improved cardiac function in diabetic mice. Mechanistically, miR-222 inhibited the endothelium to mesenchymal transition (EndMT) in diabetic mouse hearts. Mouse heart fibroblasts and endothelial cells were isolated and cultured with high glucose (HG). An miR-222 mimic did not affect HG-induced fibroblast activation and function but did suppress the HG-induced EndMT process. The antagonism of miR-222 by antagomir inhibited HG-induced EndMT. miR-222 regulated the promoter region of ß-catenin, thus negatively regulating the Wnt/ß-catenin pathway, which was confirmed by ß-catenin siRNA. Taken together, our results indicated that miR-222 inhibited cardiac fibrosis in diabetic mice via negatively regulating Wnt/ß-catenin-mediated EndMT.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose
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MicroRNAs
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Diabetes Mellitus Experimental
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Endotélio
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Beta Catenina
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Transição Epitelial-Mesenquimal
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Via de Sinalização Wnt
Limite:
Animals
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China