Protective role of p120-catenin on mitochondria by inhibiting NLRP3 in ventilator-induced lung injury.

Protective role of p120-catenin on mitochondria by inhibiting NLRP3 in ventilator-induced lung injury.
J Cell Mol Med. 2019 Sep 10;:
Authors: Liu G, Gu C, Liu M, Liu H, Wang D, Liu X, Wang Y
Abstract
Mitochondria supply energy to maintain the integrity of cell junctions. NLRP3, as the core component of the inflammatory response, is crucial in mechanical stretching. Mechanical stretching could activate NLRP3 and induce mitochondrial dysfunction. The relationship between p120 and mitochondria in ventilator-induced lung injury (VILI) has not been elucidated. MLE-12 cells and wild-type male C57BL/6 mice were pre-treated with MCC950 (specific and highly efficient inhibitor of NLRP3) or a p120 siRNA-liposome complex. Then, the cells were subjected to 20% cyclic stretching, and the mice were subjected to mechanical ventilation at a high tidal volume. Cell lysates and lung tissues were obtained to detect the expression of NLRP3, p120, TLR4 pathway components, IL-6 and IL-1β, to determine the functions and structures of mitochondria, and the wet/dry ratio of the lung, and to perform pathological staining and an Evans blue dye assay. Mechanical stretching could increase the levels of NLRP3, ROS and damaged mitochondria, while these changes could be reversed by MCC950. Moreover, p120 prevented the activation of NLRP3 and regulated NLRP3 by inhibiting the TLR4 pathway and ROS production. Additionally, p120 played a vital role in protecting mito...

Source: J Cell Mol Med - September 9, 2019 Category: Molecular Biology Authors: Liu G, Gu C, Liu M, Liu H, Wang D, Liu X, Wang Y Tags: J Cell Mol Med Source Type: research