Hypoxia-induced deregulation of miR-126 and its regulative effect on VEGF and MMP-9 expression.
Int J Med Sci
; 11(1): 17-23, 2014.
Article
en En
| MEDLINE
| ID: mdl-24396282
ABSTRACT
OBJECTIVE:
miR-126, the miRNA considered to be specially expressed in endothelial cells and hematopoietic progenitor cells, is strongly associated with angiogenesis. The purpose is to evaluate the role of miR-126 in hypoxia-induced angiogenesis and the possible mechanisms.METHODS:
The expression of miR-126 was detected in hypoxia-treated RF/6A cells and diabetic retinas using real-time PCR. The miR-126 was up- or down-regulated by transfecting miR-126-mimics or inhibitors into RF/6A cells. Cell cycle analysis was performed using flow cytometry. The protein levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were assessed by immunoblotting.RESULTS:
A significantly decreased expression of miR-126 was found in hypoxia-treated RF/6A cells in a time-dependent manner compared with normoxic condition. The expression of miR-126 was also reduced in the retina tissue of streptozotocin-induced diabetic rats. The expression of VEGF and MMP-9 proteins was increased in hypoxia-induced RF/6A cells. In the functional analysis, miR-126-mimic significantly reduced the percentage of RF/6A cells in S phases compared with the negative control under hypoxic conditions. Furthermore, the VEGF and MMP-9 protein levels were sharply decreased in hypoxia-induced RF/6A cells pretreated with miR-126-mimics and increased in the cells pretreated with miR-126-inhibitors.CONCLUSIONS:
miR-126 is down-regulated under hypoxic condition both in vitro and in vivo and may halt the hypoxia-induce neovascularization by suspending the cell cycle progression and inhibiting the expression of VEGF and MMP-9.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Hipoxia de la Célula
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Metaloproteinasa 9 de la Matriz
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MicroARNs
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Células Endoteliales
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Factor A de Crecimiento Endotelial Vascular
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Animals
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En
Año:
2014
Tipo del documento:
Article