Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

Abstract

Background Propofol, 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). Methods C57BL/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. Results Our 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. Conclusion Overall, 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.

MicroRNA-141-3p reduces pulmonary hypoxia/reoxygenation injury through suppression of Beclin-1-dependent autophagy

“…Currently, no clinical therapies are specifically designed to prevent I/R injury [ 3 ]. PMVEC injury may lead to lung endothelial barrier impairment [ 28 ], and the destruction of PMVECs may affect the normal respiratory function of the lung, thereby reducing the cellular oxygen partial pressure of the lung tissue and inducing hypoxia response [ 29 ]. Therefore, the present study constructed an in vitro cell model of H/R using PMVECs, in combination with in vivo H/R rat models, aiming to explore the effects of miR-141-3p, SIRT1 and Beclin-1 in collaboration on H/R injury of PMVECs.…”

Emerging role of long non-coding RNA MALAT1 related signaling pathways in the pathogenesis of lung disease

“…Propofol, an intravenous anaesthetic, was shown to impedes autophagy activation and secretion of inflammatory factors (e.g., TNF-α, IL-18, and IL-1β) through reducing the MALAT1-miR-144-GSK3β signaling axis. Propofol eventually alleviated lung ischemia-reperfusion in mice (Zhang et al, 2021). Although these findings imply that the use of these drugs targeting MALAT1 could be effective in treating various lung diseases, further research is necessary to fully understand their precise mechanisms of action.…”

The Impact of General Anesthesia on Redox Stability and Epigenetic Inflammation Pathways: Crosstalk on Perioperative Antioxidant Therapy

“…An experimental study carried out on laboratory animals by Zhang et al, investigating the expression of certain biological markers, such as microRNAs-144, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and glycogen synthase kinase-3β (GSK3β) in LIRI, showed that the overexpression of genes was directly proportional to the intensity of the ischemic injury. Regarding the epigenetic expression of microRNA-144, the authors reported a decrease in its concentration [ 165 ]. Li et al studied the expression of microRNA-146a in LIRI and showed a decrease in the epigenetic expression in pulmonary ischemic injury.…”