TRIM13 reduces damage to COPD alveolar epithelial cells by inhibiting ER-phagy induced by ERS

Abstract

objective Exploring the molecular mechanisms by which tripartite motif-containing protein 13 (TRIM13) regulates alveolar epithelial cell injury in Chronic Obstructive Pulmonary Disease (COPD) provides new molecular targets for the treatment of COPD. MethodDetermining the expression levels of TRIM13 in clinical patients and in a rat model of emphysema. Constructing a cigarette smoke-induced model of endoplasmic reticulum stress (ERS) and endoplasmic reticulum autophagy (ER-phagy) in A549 cells, and examining the effects of TRIM13 gene overexpression/knockdown on ERS, ER-phagy, cell apoptosis, and the PI3K/Akt/mTOR signaling pathway in A549 cells. Result The expression of TRIM13 in the lung tissues of COPD patients and emphysema rats is significantly decreased, and the level of cell apoptosis in the lung tissues of emphysema rats is significantly increased. Overexpressing TRIM13 reduces the expression levels of ERS-related molecules (GRP78, GRP94, XBP-1, and eIF2a) in COPD models; it also lowers ER-phagy levels (with a decrease in the number of autolysosomes under transmission electron microscope and an improvement in endoplasmic reticulum structure; a reduction in the expression levels of LC3 II/LC3I and Beclin1, and an increase in the expression level of the autophagy inhibitory molecule BCL-2). Furthermore, overexpressing TRIM13 activates the PI3K/Akt/mTOR signaling pathway (p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR). Conversely, knocking down TRIM13 yields opposite results. Conclusion TRIM13 attenuated alveolar epithelial cell injury in COPD by inhibiting ERS-induced ER-phagy, the mechanism of which may be activation of the PI3K/AKT/mTOR signaling pathway.