Grant: Travel Awards - Institute Community Support

Sepsis-induced ARDS accounts for 9% of all patient deaths in the ICU. As of now, there is no therapeutic treatments for this type of acute lung injury. Our work is the first in the field that combines microarray and microRNA array to identify therapeutic targets for ARDS treatment. The present study used mRNA microarray to elucidate the effects of CLP-induced sepsis and mesenchymal stem cell therapeutic treatment on the global pattern of gene expression in the murine lung. Concurrently, a microRNA array was also conducted. In the mRNA microarray, the genes that displayed significant changes between Sham operation, CLP-induced sepsis, and MSC treatment were determined with SAM analysis. While on the other hand, microRNA arrays yielded the microRNAs that exhibited the greatest fold change among the three conditions, with LIMMA analysis. By joining the SAM-selected genes with statistically significance with the targets of microRNA that had a miRSVR score greater than -0.09, we were able to identify 480 genes that satisfied the criteria. Interestingly, the angiotensin converting enzyme (ACE) was in this group of genes, which has been implicated in the pathogenesis of ARDS along with its effector peptide angiotensin (Ang) II. Our study then investigated the role of ACE in a cell model of ARDS under the treatment of our microRNA of interest which was identified to have significant fold change among the three conditions. We expect to see that ACE activity increases, matched by enhanced levels of Ang II. Therapeutic intervention using microRNA will attenuate the inflammatory mediator response, markedly decrease lung injury scores, and improve lung function. This microarray-microRNA array approach yields a highly informed method in identifying potetial therapeutic targets, as well as the microRNA that could be employed to regulate the level of gene expression. Our findings provides new insight to the therapeutic treatment of ARDS.