BME Investigators Use MicroRNAs to Regulate Lung Inflammation during Mechanical Ventilation
Samir Ghadiali, BME Associate Professor, in collaboration with Patrick Nana-Sinkam, MD, Associate Professor of Internal Medicine and Co-Director of Research Programs in the Division of Pulmonary Allergy, Critical Care and Sleep Medicine, has discovered a new way to regulate the excessive inflammation caused by mechanical ventilators. Patients with severe pulmonary infections, i.e. Acute Lung Injury, often require mechanical or artificial ventilation. Unfortunately, these ventilators generate mechanical forces that can exacerbate lung and systemic inflammation which leads to multi-organ failure. Despite intense research, scientists currently do not know how to regulate this type of mechanically-induced inflammation and as a result, Acute Lung Injury kills more people in the U.S. than breast and prostate cancer combined.
Recently, microRNAs have emerged as an important class of small molecules that can regulate physiological processes including cancer metastasis and angiogenesis. In this study, the authors sought to identify the role microRNAs play in regulating mechanically-induced inflammation in the lung. The authors demonstrated that mechanical forces not only alter microRNA expression patterns in lung epithelia but they also demonstrated that a specific microRNA, miR-146a, can regulate mechanically-induced inflammation. Specifically, over-expressing miR-146a reduced pro-inflammatory cytokines production in epithelial cells exposed to mechanical pressure. The authors also demonstrated for the first time that molecular components of the innate immune system (TLRs) play a role in the conversion of mechanical forces into biochemical/gene signals. The clinical implications of this study are that pharmaceutical manipulation of miR-146a might represent a novel way to regulate lung inflammation in mechanically ventilated patients even after the initial bacterial/viral insult has been cleared.
This research study was supported by grants from the NSF, NIH and American Heart Association and was published in The Journal of the Federation of American Societies for Experimental Biology (FASEB), which is the 3rd ranked Biology journal and a leading Cell Biology journal. BME authors include Dr. Yan Huang, post-doctoral research scientist, Natalia Higuita-Castro, PhD candidate in BME and Dr. Ghadiali.
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