Abstract
BackgroundPropofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β).MethodsC57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured.ResultsOur experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression.ConclusionOverall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.
Highlights
Lung ischemia/reperfusion (I/R) injury is a primary cause of dysfunction in pulmonary grafts, which plays a significant role in lung disease treatment (Wu et al 2015)
Compared with the I/R group, PaO2 was increased while W/D ratio was decreased in mice of the I/R + Propofol group (Fig. 1B, C)
tumor necrosis factor-α (TNF-α), IL-1β, and IL-18 levels were reduced in the cells of the H/R + oe-negative control (NC) + Propofol group, but elevated by overexpressing gen synthase kinase-3β (GSK3β) (Fig. 5H). These results indicated that overexpressed GSK3β promoted the activation of autophagy and release of inflammatory factors to reverse the protective effects of Propofol on H/R cells
Summary
Lung ischemia/reperfusion (I/R) injury is a primary cause of dysfunction in pulmonary grafts, which plays a significant role in lung disease treatment (Wu et al 2015). Zhang et al Mol Med (2021) 27:77 respiratory function of the lungs, reducing cellular oxygen partial pressure of the lung tissues and causing the body to initiate a hypoxic response (Sharma et al 2018). The specific role of autophagy in lung I/R injury has still not been adequately studied. An intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mecha‐ nisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glyco‐ gen synthase kinase-3β (GSK3β)
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