"Hypoxia-induced down-regulation of microRNA-449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA - a mechanism involved in SERPINE1 (PAI-1) overexpression".
J Transl Med
; 8: 33, 2010 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-20356416
ABSTRACT
BACKGROUND:
In damaged organs tissue repair and replacement of cells by connective tissue provokes a response of fibroblasts to cellular stress factors such as hypoxia.MicroRNAs (miRNA) are small non-coding RNA molecules which bind to their mRNA targets which eventually lead to repression of translation. Whether the response of fibroblasts to stress factors also involves the miRNA system is largely unknown.RESULTS:
By miRNA profiling we identified down-regulation of miRNA-449a/b expression in hypoxic fibroblasts. Specific miRNA inhibitors and mimics showed direct evidence for targeting the serine protease inhibitor (serpin) protein (SERPINE1; plasminogen activator inhibitor-1, PAI-1) by miRNA-449a/b leading to SERPINE1 mRNA and protein up- and down-regulation, respectively. SERPINE1 expression in vivo could be located predominantly in areas of fibrosis and remodeling.CONCLUSIONS:
Our study offers serious lines of evidence for a novel hypoxia-dependent mechanism involving hypoxia-induced decrease of clustered miRNA-449a/b, hypoxia-induced amplification of concomitant increase of targeted SERPINE1 (PAI-1) and its overexpression in tissues showing a hypoxic environment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
Inhibidor 1 de Activador Plasminogénico
/
MicroARNs
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Hipoxia
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Transl Med
Año:
2010
Tipo del documento:
Article
País de afiliación:
Alemania