The Role of MicroRNAs in Acute Respiratory Distress Syndrome and Sepsis, From Targets to Therapies: A Narrative Review

Acute respiratory distress syndrome (ARDS) is a significant cause of morbidity and mortality in the intensive care unit (ICU) and is characterized by lung epithelial and endothelial cell injury, with increased permeability of the alveolar-capillary membrane, leading to pulmonary edema, severe hypoxia, and difficulty with ventilation. The most common cause of ARDS is sepsis, and currently, treatment of ARDS and sepsis has consisted mostly of supportive care because targeted therapies have largely been unsuccessful. The molecular mechanisms behind ARDS remain elusive. Recently, a number of microRNAs (miRNAs) identified through high-throughput screening studies in ARDS patients and preclinical animal models have suggested a role for miRNA in the pathophysiology of ARDS. miRNAs are small noncoding RNAs ranging from 18 to 24 nucleotides that regulate gene expression via inhibition of the target mRNA translation or by targeting complementary mRNA for early degradation. Unsurprisingly, some miRNAs that are differentially expressed in ARDS overlap with those important in sepsis. In addition, circulatory miRNA may be useful as biomarkers or as targets for pharmacologic therapy. This can be revolutionary in a syndrome that has neither a measurable indicator of the disease nor a targeted therapy. While there are currently no miRNA-based therapies targeted for ARDS, therapies targeting miRNA have reached phase II clinical trials for the treatment of a wide range of diseases. Further studies may yield a unique miRNA profile pattern that serves as a biomarker or as targets for miRNA-based pharmacologic therapy. In this review, we discuss miRNAs that have been found to play a role in ARDS and sepsis, the potential mechanism of how particular miRNAs may contribute to the pathophysiology of ARDS, and strategies for pharmacologically targeting miRNA as therapy.