Bone marrow‐derived mesenchymal stem cells enhance autophagy via PI3K/AKT signalling to reduce the severity of ischaemia/reperfusion‐induced lung injury

Abstract

Autophagy, a type II programmed cell death, is essential for cell survival under stress, e.g. lung injury, and bone marrow-derived mesenchymal stem cells (BM-MSCs) have great potential for cell therapy. However, the mechanisms underlying the BM-MSC activation of autophagy to provide a therapeutic effect in ischaemia/reperfusion-induced lung injury (IRI) remain unclear. Thus, we investigate the activation of autophagy in IRI following transplantation with BM-MSCs. Seventy mice were pre-treated with BM-MSCs before they underwent lung IRI surgery in vivo. Human pulmonary micro-vascular endothelial cells (HPMVECs) were pre-conditioned with BM-MSCs by oxygen-glucose deprivation/reoxygenation (OGD) in vitro. Expression markers for autophagy and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signalling pathway were analysed. In IRI-treated mice, administration of BM-MSCs significantly attenuated lung injury and inflammation, and increased the level of autophagy. In OGD-treated HPMVECs, co-culture with BM-MSCs attenuated endothelial permeability by decreasing the level of cell death and enhanced autophagic activation. Moreover, administration of BM-MSCs decreased the level of PI3K class I and p-Akt while the expression of PI3K class III was increased. Finally, BM-MSCs-induced autophagic activity was prevented using the inhibitor LY294002. Administration of BM-MSCs attenuated lung injury by improving the autophagy level via the PI3K/Akt signalling pathway. These findings provide further understanding of the mechanisms related to BM-MSCs and will help to develop new cell-based therapeutic strategies in lung injury.

Hepatic miR‐125b inhibits insulin signaling pathway by targeting PIK3CD

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Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions

“…In damaged liver cells, MSC ameliorated liver fibrosis via activating autophagy, and human placenta‐derived mesenchymal stem cells also promoted hepatic regeneration by up‐regulating HIF‐1α and activating autophagy . BMSCs also attenuated lung injury by increasing the autophagy level via the PI3K/Akt signalling pathway . In this study, coculturing with BMSCs induced more intense autophagy than that in the hypoxia group.…”

“…Differentiation was also found to be another important aspect, as the transplanted BMSCs expressed several functional cell markers; however, the functions of the differentiated cells remain controversial . Recently, studies have shown that BMSCs can regulate autophagy …”

“…Mechanisms underlying the effects of BMSCs include but were not limited to their ability to express a variety of cytokines and neurotrophic factors . BMSCs were also reported to actively participate in autophagy to ameliorate ischaemia/reperfusion‐induced lung injury and liver fibrosis . More important, BMSCs were reported to protect ischaemic retina by increasing autophagy .…”

Mesenchymal stem cells enhance autophagy of human intrahepatic biliary epithelial cells in vitro

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