Kun He1, Shuang Han2, Li An3, Jin Zhang1. 1. Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, No. 206, Zhongshan East Road, Shijiazhuang, 050011, Hebei, China. 2. Department of Anesthesiology, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, 050051, Hebei, China. 3. Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, No. 206, Zhongshan East Road, Shijiazhuang, 050011, Hebei, China. a20200408sci@126.com.
Abstract
PURPOSE: Ventilator-induced lung injury (VILI) is an additional inflammatory injury caused by mechanical ventilation (MV). This study aimed to determine the effects of microRNA-214 (miR-214) on VILI and its underlying mechanism of action. METHODS: To develop a VILI mouse model, mice were subjected to MV. The expression of miR-214 was detected by qRT-PCR. The macrophages, fibroblasts, epithelial cells, and endothelial cells were isolated from lung tissues by fluorescence-activated cell sorting. The histopathological changes of lung, lung wet/dry weight (W/D) ratio, and myeloperoxidase (MPO) activity were used to evaluate the degree of lung injury. The levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was performed to determine the interactions between miR-214 and FGFR1. Western blot was used to detect the protein expression of FGFR1, p-AKT, and p-PI3K. RESULTS: The expression of miR-214 was increased in lung tissues and macrophages, fibroblasts, epithelial cells, and endothelial cells isolated from lung tissues in VILI mice. MiR-214 inhibition decreased the histopathological changes of lung, lung W/D ratio, MPO activity, and pro-inflammatory cytokines levels in BALF in VILI mice. FGFR1 was targeted by miR-214. The protein expression of FGFR1 was decreased in VILI mice. Ponatinib (FGFR1 inhibitor) reversed the suppressive effects of miR-214 inhibition on lung injury and inflammation of VILI mice. MiR-214 increased the activity of PI3K/AKT pathway by regulating FGFR1. CONCLUSIONS: Inhibition of miR-214 attenuated lung injury and inflammation in VILI mice by increasing FGFR1 expression, providing a novel therapeutic target for VILI.
PURPOSE: Ventilator-induced lung injury (VILI) is an additional inflammatory injury caused by mechanical ventilation (MV). This study aimed to determine the effects of microRNA-214 (miR-214) on VILI and its underlying mechanism of action. METHODS: To develop a VILI mouse model, mice were subjected to MV. The expression of miR-214 was detected by qRT-PCR. The macrophages, fibroblasts, epithelial cells, and endothelial cells were isolated from lung tissues by fluorescence-activated cell sorting. The histopathological changes of lung, lung wet/dry weight (W/D) ratio, and myeloperoxidase (MPO) activity were used to evaluate the degree of lung injury. The levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was performed to determine the interactions between miR-214 and FGFR1. Western blot was used to detect the protein expression of FGFR1, p-AKT, and p-PI3K. RESULTS: The expression of miR-214 was increased in lung tissues and macrophages, fibroblasts, epithelial cells, and endothelial cells isolated from lung tissues in VILI mice. MiR-214 inhibition decreased the histopathological changes of lung, lung W/D ratio, MPO activity, and pro-inflammatory cytokines levels in BALF in VILI mice. FGFR1 was targeted by miR-214. The protein expression of FGFR1 was decreased in VILI mice. Ponatinib (FGFR1 inhibitor) reversed the suppressive effects of miR-214 inhibition on lung injury and inflammation of VILI mice. MiR-214 increased the activity of PI3K/AKT pathway by regulating FGFR1. CONCLUSIONS: Inhibition of miR-214 attenuated lung injury and inflammation in VILI mice by increasing FGFR1 expression, providing a novel therapeutic target for VILI.
Authors: Duaa Dakhlallah; Kara Batte; Yijie Wang; Carmen Z Cantemir-Stone; Pearlly Yan; Gerard Nuovo; Adel Mikhail; Charles L Hitchcock; Valerie P Wright; S Patrick Nana-Sinkam; Melissa G Piper; Clay B Marsh Journal: Am J Respir Crit Care Med Date: 2013-01-10 Impact factor: 21.405
Authors: Wen Lu; Ran You; Xiaoyi Yuan; Tianshu Yang; Errol L G Samuel; Daniela C Marcano; William K A Sikkema; James M Tour; Antony Rodriguez; Farrah Kheradmand; David B Corry Journal: Nat Immunol Date: 2015-10-05 Impact factor: 25.606