Autophagy protects against ischemia/reperfusion-induced lung injury through alleviating blood–air barrier damage

Zhang, Dan; Li, Chichi; Zhou, Jian; Song, Yuanlin; Fang, Xuekun; Ou, Jiaxian; Li, Jing; Bai, Chunxue

doi:10.1016/j.healun.2014.12.008

Cited by 33 publications

(36 citation statements)

References 21 publications

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“…Left lung IRI operations were performed as previously described 14,15. A total of 5 × 10 5 BM-MSCs suspended in 100 μl of PBS or the same volume of PBS without BM-MSCs was injected via the tail vein 1 hr before surgery.…”

Section: Methodsmentioning

confidence: 99%

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

Zhou

Zhang

et al. 2015

J Cellular Molecular Medi

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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.

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Section: Methodsmentioning

confidence: 99%

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

Zhou

Zhang

et al. 2015

J Cellular Molecular Medi

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“…Furthermore, autophagy serves a protective role in LIRI (15). However, in a previous study indicated that autophagy was activated and served a role in the pathophysiological process of LIRI (16).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine preconditioning protects against lung injury induced by ischemia-reperfusion through inhibition of autophagy

Zhang

2017

Experimental and Therapeutic Medicine

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The present study aimed to evaluate the role of autophagy in the protective effect of dexmedetomidine in lung injury caused by ischemia-reperfusion (IR) in rats. In total 48 adult male Sprague-Dawley rats were randomly divided into 6 groups (n=8) as follows: i) Sham group; ii) the IR group; iii) IR + 1 µg/kg dexmedetomidine preconditioning group (pre-LD); iv) IR + 10 µg/kg dexmedetomidine preconditioning group (pre-HD); v) IR + 1 µg/kg dexmedetomidine postconditioning group (post-LD); and vi) IR + 10 µg/kg dexmedetomidine postconditioning group (post-HD). After the rats were anesthetized, the hilum of the left lung was occluded with a non-invasive microvascular clip for 30 min to induce ischemia. The clip was then removed and the left lung was allowed to regain ventilation and blood for 2 h. The rats were then sacrificed, the left lung removed and the wet/dry (W/D) lung weight ratio was determined. Pathological changes to the lungs were evaluated by light and transmission electron microscopy. Furthermore, the rate of lung cell apoptosis was determined by the TUNEL assay. The expression of hypoxia-inducible factor 1α (HIF-1α), Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), BNIP3 like (BNIP3 L) and microtubule-associated protein 1A/1B light chain 3B (LC3II) was determined by western blotting. Compared with the sham group, a significant increase in the W/D lung weight ratio, and malondialdehyde (MDA), BNIP3, BNIP3 L and LC3II levels were observed in the IR group, and HIF-1α levels and superoxide dismutase (SOD) activity were decreased. Furthermore, the W/D ratio was lower in the pre-LD and pre-HD groups than in the IR group. Additionally, SOD activity was significantly higher and MDA expression was significantly lower in the pre-LD and pre-HD groups compared with the IR group. BNIP3, BNIP3 L and LC3II protein levels were significantly lower in the pre-LD and pre-HD groups compared with the IR group, while HIF-1α was notably upregulated in the pre-LD and pre-HD groups compared with the IR group. In conclusion, the results of the present study indicate that dexmedetomidine preconditioning protects against lung injury induced by IR through inhibition of autophagy and apoptosis.

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“…For example, low doses of rapamycin exert negligible immunosuppressive effects, whereas high doses have significant anti-inflammatory effects and even facilitate the transformation of normal cells into tumor cells [21, 22]. In previous studies, we found that low doses of rapamycin could effectively induce autophagy and reduce death and damage in pulmonary microvascular endothelial cells in an ischemic microenvironment in vitro [14]. In this study, we used a low dose of rapamycin.…”

Section: Discussionmentioning

confidence: 99%

“…According to our previous study [14], 10 nmol/L of rapamycin (LC Laboratories) was added into the culture medium, and the cells were subsequently incubated for 4 h before they were challenged with OGD.…”

Section: Methodsmentioning

confidence: 99%

“…An OGD method was used to simulate an ischemic microenvironment in vitro according to a previous study [14]. The cells were subjected to OGD by replacing the adipogenic medium with DMEM deprived of glucose and fetal calf serum and then placed in an anaerobic chamber (5% CO 2 /95% N 2 ; BioSpherix, C-174) at 37°C for 8 h, and then the cells were collected for further experiments.…”

Section: Methodsmentioning

confidence: 99%

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Rapamycin Promotes the Survival and Adipogenesis of Ischemia-Challenged Adipose Derived Stem Cells by Improving Autophagy

Yang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Ischemia is one of the main causes of the high rate of absorption of transplanted autologous fat. Autophagy allows cells to survive by providing energy under starvation. Rapamycin has been found to play a role in promoting autophagy. In this study, we investigated whether rapamycin participates in the survival and adipogenesis of ischemia-challenged adipose-derived stem cells (ADSCs) by regulating autophagy. Methods: Before the cells were exposed to oxygen-glucose deprivation (OGD), a simulated ischemic microenvironment, the level of autophagy was reduced or increased by lentiviral transfection with short hairpin RNA targeting microtubule-associated protein 1-light chain 3 gene (shRNA-LC3) or treatment with rapamycin, respectively. The level of autophagy was assessed by western blotting, transmission electron microscopythen the apoptosis ratio was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and flow cytometry. Adipogenesis was further evaluated by oil red O staining and the expressions level of some specific proteins for adipocytes. Results: shRNA-LC3 and rapamycin treatment effectively decreased and improved the level of autophagy in cells with or without OGD challenge, respectively. In addition, autophagy inhibition increased the apoptosis rate and activated caspase-3 expression level in response to OGD, and these were markedly inhibited by rapamycin preconditioning. During adipogenesis, autophagy inhibition decreased not only oil droplet accumulation but also lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor gamma (PPARγ) expression in cells with or without OGD challenge. However, autophagy promotion by rapamycin increased oil droplet accumulation and LPL and PPARγ expression. Conclusions: Rapamycin may promote the survival and adipogenesis of ischemia-challenged ADSCs by upregulating autophagy.

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Autophagy protects against ischemia/reperfusion-induced lung injury through alleviating blood–air barrier damage

Cited by 33 publications

References 21 publications

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

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

Dexmedetomidine preconditioning protects against lung injury induced by ischemia-reperfusion through inhibition of autophagy

Rapamycin Promotes the Survival and Adipogenesis of Ischemia-Challenged Adipose Derived Stem Cells by Improving Autophagy

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