MicroRNA expression following activated protein C treatment during septic shock

作者：Moore Cathy C; McKillop Iain H; Toan Huynh^*

来源：Journal of Surgical Research, 2013, 182(1): 116-126.

DOI：10.1016/j.jss.2012.07.063

• Sepsis
• Activated protein C
• Microarray
• Bioinformatics

Background: Sepsis induces systemic stress by augmenting inflammatory and procoagulant responses, resulting in microvascular dysfunction and end organ failure, events modulated by the protein C pathway. MicroRNAs (miRNAs) are small noncoding RNAs involved in post-transcriptional regulation of genes; yet, their role in sepsis is poorly defined. We hypothesized that activated protein C (aPC) selectively alters specific miRNA expression implicated in protection of hepatic function during septic shock.
Methods: Male Sprague-Dawley rats underwent sham or cecal ligation and puncture surgery; 24 h later, we randomized them to aPC (1 mg/kg) or vehicle (0.9% [w/v] saline) treatment via an indwelling venous catheter (12-h intervals for 24 h). We performed gene array and quantitative reverse transcriptaseepolymerase chain reaction analysis on hepatic RNA to determine miRNA expression and determined predicted mRNA targets using a bioinformatics approach. We confirmed beneficial effects of aPC treatment in the cecal ligation and puncture model of sepsis by survival and blood chemistries, and histologically.
Results: Of 351 rat miRNAs examined, 17 were highly expressed during sepsis and restored to basal levels after aPC treatment. We confirmed expression of select miRNAs (miR-182, -199a-5p, -203, -211, -222, and -29b) using quantitative reverse transcriptaseepolymerase chain reaction. In silico analysis identified nine miRNAs significantly regulating target genes of the focal adhesion pathway.
Conclusions: These data suggest that aPC treatment coordinates beneficial cytoprotective effects during sepsis by modulating miRNA expression. Whereas translational effects remain to be fully elucidated in a clinical setting, we demonstrate here the potential experimental and computational benefits of using of microRNA analysis in sepsis.

• 出版日期2013-6-1