tailieunhanh - Báo cáo hóa học: " “Hypoxia-induced down-regulation of microRNA449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA - a mechanism involved in SERPINE1 (PAI-1) overexpression”

“Hypoxia-induced down-regulation of microRNA449a/b impairs control over targeted SERPINE1 (PAI-1) mRNA - a mechanism involved in SERPINE1 (PAI-1) overexpression” | Muth et al. Journal of Translational Medicine 2010 8 33 http content 8 1 33 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Hypoxia-induced down-regulation of microRNA-449a b impairs control over targeted SERPINE1 PAI-1 mRNA - a mechanism involved in SERPINE1 PAI-1 overexpression 1 1 1 2 11 Michaela Muth Katharina Theophile Kais Hussein Christoph Jacobi Hans Kreipe Oliver Bock 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. Background Extracellular matrix ECM deposition and fibrotic remodeling in damaged tissues is the principle to regain integrity when affected tissues have no or only limited capability for self-renewal 1 . Damage of tissues and cells can be induced by hypoxia infections and chronic irritants but has in common that the response to injury is very similar. Mechanisms of reparation will take place .