MiR-155 alleviates septic lung injury by inducing autophagy via inhibition of transforming growth factor-β-activated binding protein 2
F Liu, C Nie, N Zhao, Y Wang, Y Liu, Y Li, Z Zeng… - Shock, 2017 - journals.lww.com
F Liu, C Nie, N Zhao, Y Wang, Y Liu, Y Li, Z Zeng, C Ding, Q Shao, C Qing, L Xia, Z Peng…
Shock, 2017•journals.lww.comBackground: The anti-inflammatory effect of miR-155 was closely linked to transforming
growth factor-β-activated kinase-1-binding protein 2 (TAB2) and autophagy. This study
investigated the role of miR-155 in attenuation of septic lung injury through TAB2 and
autophagy in mouse model and in vitro. Methods: Patients who underwent fiberoptic
bronchoscope examination with or without septic lung injury were recruited for the collection
of bronchoalveolar lavage fluid (BALF) samples. Mouse model of septic lung injury was …
growth factor-β-activated kinase-1-binding protein 2 (TAB2) and autophagy. This study
investigated the role of miR-155 in attenuation of septic lung injury through TAB2 and
autophagy in mouse model and in vitro. Methods: Patients who underwent fiberoptic
bronchoscope examination with or without septic lung injury were recruited for the collection
of bronchoalveolar lavage fluid (BALF) samples. Mouse model of septic lung injury was …
Abstract
Background:
The anti-inflammatory effect of miR-155 was closely linked to transforming growth factor-β-activated kinase-1-binding protein 2 (TAB2) and autophagy. This study investigated the role of miR-155 in attenuation of septic lung injury through TAB2 and autophagy in mouse model and in vitro.
Methods:
Patients who underwent fiberoptic bronchoscope examination with or without septic lung injury were recruited for the collection of bronchoalveolar lavage fluid (BALF) samples. Mouse model of septic lung injury was established by cecal ligation puncture, while alveolar macrophage cell line was treated with lipopolysaccharide (LPS). Agomir miR-155 transfection into the mouse airways was performed to induce miR-155 expression, while miR-155 mimic, miR-155 inhibitor, or TAB2-siRNA was transfected into NR8383 macrophages. Mouse BALF and cell cytokine levels, lung tissue pathology and wet/dry ratio, numbers of autophagy bodies, miR-155, gene and protein expressions were also examined accordingly.
Results:
Expression of miR-155 was increased in the BALF of septic lung injury patients, in mouse model and NR8383 macrophages after LPS treatment. Increased numbers of autophagy bodies were also observed in mouse and macrophage models. MiR-155-transfected mice showed alleviation of inflammation, lower water content in lung tissues, increased number of autophagy bodies, increased expression of microtubule-associated protein 1 light chain 3 (LC3 II/I), reduced expressions of cysteinyl aspartate-specific protease-1 (Caspase-1), and TAB2, and decreased cytokines levels. Similar results were obtained in macrophages after LPS treatment. Cells transfected with miR-155 inhibitor showed increased expression of TAB2 and Caspase-1, fewer autophagy bodies, lower LC3 II/I expression, and higher cytokine levels.
Conclusion:
The current study observed a higher level of miR-155 in the BALF from sepsis patients with acute respiratory distress syndrome and demonstrated that miR-155 alleviated inflammation in septic lung injury in mouse and cell models by inducing autophagy via inhibition of TAB2.
Lippincott Williams & Wilkins