RESUMEN
Long noncoding RNAs (lncRNAs) have been reported to serve a key role in a variety of cardiovascular diseases, including in cardiac fibrosis. The present study aimed to investigate the biological role and underlying mechanisms of the induction of cardiac fibroblasts by the lncRNA, RNA component of mitochondrial RNA processing endoribonuclease (RMRP). The results demonstrated that RMRP expression was upregulated in the presence of cardiac fibrosis in an abdominal aortic bandingtreated rat model. Treatment with angiotensin II increased RMRP expression in cardiac fibroblasts, while the knockdown of RMRP by smallinterfering RNA inhibited cardiac fibroblast proliferation, differentiation and collagen accumulation. To further investigate the underlying mechanisms of this interaction, microRNA (miR)613 was predicted to be a target miR of RMRP and sequence alignment, luciferase activity and MS2 RNA immunoprecipitation were performed to detect the interaction between RMRP and miR613. The results suggested that RMRP negatively regulated miR613 in cardiac fibroblasts. Furthermore, miR613 was indicated to mediate the promoting effect of RMRP on cardiac fibroblast activation. The current study suggested that RMRP promoted cardiac fibroblast activation by acting as a competing endogenous RNA for miR613. Therefore, RMRP may be a novel target for the prevention or treatment of cardiac ï¬brosis.
Asunto(s)
Fibroblastos/metabolismo , MicroARNs/genética , Miocardio/metabolismo , ARN Largo no Codificante/genética , Regulación hacia Arriba , Animales , Células Cultivadas , Endorribonucleasas/genética , Fibroblastos/citología , Fibroblastos/patología , Fibrosis , Masculino , Miocardio/citología , Miocardio/patología , Ratas Sprague-DawleyRESUMEN
AIMS: To evaluate the efficacy, tolerability, and safety of long-acting versus standard non-ergot dopamine agonists (NEDAs) in Parkinson's disease (PD), we performed a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: The PubMed, EMBASE, Cochrane Library databases, and Web of Knowledge were searched up to November 20th 2013. The pooled weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Eight large-scale RCTs, involving 2402 patients, were included in this meta-analysis. Compared with the standard NEDAs, long-acting NEDAs exhibited similar improvements in Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score (WMD 0.09, 95% CI -0.33 to 0.50), motor score (WMD -0.35, 95% CI -1.60 to 0.90), and "off" time (WMD 0.18, 95% CI -0.14 to 0.50). No differences were found in overall withdrawals (RR 1.11, 95% CI 0.94 to 1.32), withdrawals due to adverse events (RR 1.19, 95% CI 0.91 to 1.56), or the ten commonly reported adverse events between the two formulations. CONCLUSIONS: Our meta-analysis showed long-acting NEDAs were noninferior to standard NEDAs in efficacy, tolerability, and safety in the treatment of PD.