miR-127 contributes to ventilator-induced lung injury

Abstract

Although it is essential in critical care medicine, mechanical ventilation often results in ventilator-induced lung injury (VILI). Treating mice with lipopolysaccharide has been reported to upregulate the expression of miR-127, which has been implicated in the modulation of immune responses. However, the putative roles of miR-127 during the development of VILI have yet to be elucidated. The present study demonstrated that challenging mice with mechanical ventilation for 6 h significantly upregulated the expression of miR-127 in bronchoalveolar lavage fluid, serum and lung tissue samples. Conversely, following the downregulation of miR-127 expression in vivo using an adenovirus delivery system, VILI-associated pathologies, including alterations in the pulmonary wet/dry ratio, pulmonary permeability, lung neutrophil infiltration and levels of pro-inflammatory cytokines, were significantly attenuated. In addition, miR-127 knockdown inhibited the ventilation-induced activation of nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). These findings suggested that the upregulation of miR-127 expression may contribute to the development of VILI, through the modulation of pulmonary permeability, the induction of histopathological alterations, and the potentiation of inflammatory responses involving NF-κB and p38 MAPK-associated signaling pathways.