scholarly journals Autophagy Regulates the Effects of Adipose-Derived Stem Cell Small Extracellular Vesicles On Lipopolysaccharide-Induced Pulmonary Microvascular Barrier Damage

2022 ◽  
Author(s):  
Chichi Li ◽  
Min Wang ◽  
Wangjia Wang ◽  
Yuping Li ◽  
Dan Zhang
Keyword(s):  
Stem Cell ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Extracellular Vesicles ◽  
Tissue Injury ◽  
Stem Cell Differentiation ◽  
Microvascular Endothelial Cell ◽  
Target Cells ◽  
Autophagy Inhibition

Abstract Background: Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived sEVs (ADSC-sEVs) and autophagy-mediated regulation of ADSC-sEVs in LPS-induced pulmonary microvascular barrier damage remains unclear. Methods: After treatment with sEVs from ADSCs with or without autophagy inhibition, LPS-induced human pulmonary microvascular endothelial cell (HPMVECs) barrier damage was detected. LPS-induced acute lung injury in mice was assessed in vivo after intravenous administration of sEVs from ADSCs with or without autophagy inhibition. The effects of autophagy on the bioactive miRNA components of ADSC-sEVs were assessed after prior inhibition of cell autophagy. Results: We found that ADSC-sEV effectively alleviated LPS-induced apoptosis, tight junction damage and high permeability of PMVECs. Moreover, in vivo administration of ADSC-sEV markedly inhibited LPS-triggered lung injury. However, autophagy inhibition, markedly weakened the therapeutic effect of ADSC-sEVs on LPS-induced PMVECs barrier damage and acute lung injury. In addition, autophagy inhibition, prohibited the expression of five specific miRNAs in ADSC-sEVs -under LPS-induced inflammatory conditions. Conclusions: Our results indicate that ADSC-sEVs protect against LPS-induced pulmonary microvascular barrier damage and acute lung injury. Autophagy is a positive mediator of sEVs function, at least in part through controlling the expression of bioactive miRNAs in sEVs.

Autophagy Regulates the Effects of Adipose-derived Stem Cells Exosomes on Lipopolysaccharide-induced Pulmonary Microvascular Barrier Damage

2021 ◽  
Author(s):  
Chichi Li ◽  
Liqun Li ◽  
Min Wang ◽  
Wangjia Wang ◽  
Yuping Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Lung Injury ◽  
Tissue Repair ◽  
Tissue Injury ◽  
Stem Cell Differentiation ◽  
Target Cells ◽  
Adipose Derived Stem Cells ◽  
Pretreatment Effects ◽  
Autophagy Inhibition

Abstract Background: Exosomes have been recognized as being more effective than direct stem cell differentiation into functional target cells for protecting against tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived exosomes (ADSC-Exos) and autophagy-mediated regulation of ADSC-Exos in LPS-induced pulmonary microvascular barrier damage remain unclear. Methods: LPS-induced pulmonary microvascular barrier injury was detected after ADSC-Exos pretreatment. Effects of autophagy on the function and bioactive miRNAs components of ADSC-Exos were assessed after inhibiting the cells autophagy in advance. Results: ADSC-Exo culture resulted in significant alleviation of LPS-induced microvascular barrier injury. The inhibition of autophagy markedly weakened the therapeutic effect of ADSC-Exos. In addition, autophagy inhibition changed the expression levels of the five specific miRNAs in exosomes; interleukin-1β（IL-1β）preconditioning promoted the expression of miR(miRNA)-21a but lowered the expressions of let-7-a-1, miR-143 and miR-145a, and did not affect the expression of miR-451a. Autophagy inhibition, however, has prohibited the expressions of all these miRNAs under IL-1β preconditioning. Conclusion: Our results indicate that ADSC-Exos protect against LPS-induced pulmonary microvascular barrier damage. Autophagy is a positive mediator of exosome function at least partly through controlling the expression of bioactive miRNAs in exosomes.

scholarly journals Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action

2012 ◽  
Vol 303 (11) ◽  
pp. L967-L977 ◽  
Author(s):  
Lavinia Ionescu ◽  
Roisin N. Byrne ◽  
Tim van Haaften ◽  
Arul Vadivel ◽  
Rajesh S. Alphonse ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Conditioned Medium ◽  
Lung Fibroblasts ◽  
Lung Injury Score ◽  
M2 Macrophage ◽  
Arginase 1 ◽  
Igf I

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 “healer” phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I.

scholarly journals Osthole Protects against Acute Lung Injury by Suppressing NF-κB-Dependent Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yiyi Jin ◽  
Jianchang Qian ◽  
Xin Ju ◽  
Xiaodong Bao ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Nuclear Translocation ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Peritoneal Macrophages ◽  
Anti Inflammatory

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In this study, we investigated whether osthole ameliorates inflammatory sepsis-related ALI. Results from in vitro studies indicated that osthole treatment inhibited the LPS-induced inflammatory response in mouse peritoneal macrophages through blocking the nuclear translocation of NF-κB. Consistently, the in vivo studies indicated that osthole significantly prolonged the survival of septic mice which was accompanied by inflammation suppression. In the ALI mouse model, osthole effectively inhibited the development of lung tissue injury, leukocytic recruitment, and cytokine productions, which was associated with inhibition of NF-κB nuclear translocation. These findings provide evidence that osthole was a potent inhibitor of NF-κB and inflammatory injury and suggest that it could be a promising anti-inflammatory agent for therapy of septic shock and acute lung injury.

Downregulation of blood and bone marrow neutrophils decreases expression of acute lung injury in sheep

1992 ◽  
Vol 263 (5) ◽  
pp. H1492-H1498
Author(s):  
P. J. McKenna ◽  
D. L. Rosolia ◽  
Y. Ishihara ◽  
K. H. Albertine ◽  
N. C. Staub ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Peripheral Blood ◽  
Pulmonary Circulation ◽  
Tissue Injury ◽  
Blood Neutrophils ◽  
Superoxide Release

We have shown that infusion of zymosan-activated plasma (ZAP) in sheep causes acute lung injury and downregulates peripheral blood neutrophils in that elicited superoxide release is reduced for at least 24 h after the infusion. The present study was designed to test the following hypotheses: 1) peripheral blood neutrophils are representative of neutrophils marginated in the pulmonary circulation, 2) blood neutrophils are downregulated because neutrophils developing in bone marrow are similarly affected, and 3) downregulated neutrophils have a reduced capacity to produce tissue injury. In a series of experiments in 21 sheep, we showed that elicited superoxide release was similar in peripheral blood neutrophils and in marginated neutrophils washed out of the pulmonary vascular bed. Measurements of superoxide release from blood and bone marrow neutrophils collected 2-24 h after ZAP infusion revealed progressive downregulation with time and greater downregulation of superoxide release in bone marrow neutrophils compared with peripheral blood neutrophils. Finally, after downregulating peripheral blood neutrophils, subsequent infusion of ZAP in conscious sheep produced sequestration of neutrophils in the pulmonary circulation but failed to produce a sustained increase in lung lymph protein clearance. The results suggest that neutrophil downregulation, as measured in vitro, is expressed in vivo as reduced ability of neutrophils to produce tissue injury when challenged by an activating agent.

scholarly journals Therapeutic use of mesenchymal stem cell-derived extracellular vesicles in acute lung injury

Transfusion ◽  
2018 ◽  
Vol 59 (S1) ◽  
pp. 876-883 ◽  
Author(s):  
Jae Hoon Lee ◽  
Jeonghyun Park ◽  
Jae-Woo Lee
Keyword(s):  
Stem Cell ◽  
Acute Lung Injury ◽  
Mesenchymal Stem Cell ◽  
Lung Injury ◽  
Extracellular Vesicles ◽  
Therapeutic Use

scholarly journals Platelet Extracellular Vesicles mediate Transfusion-related Acute Lung Injury by imbalancing the Sphingolipid Rheostat

Blood ◽  
2020 ◽  
Author(s):  
Mark J McVey ◽  
Sarah Weidenfeld ◽  
Mazharul Maishan ◽  
Chris Spring ◽  
Michael Kim ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Extracellular Vesicles ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Platelet Storage ◽  
Barrier Failure ◽  
Long Chain

Transfusion-related acute lung injury (TRALI) is a hazardous transfusion complication with an associated mortality of 5-15%. We previously showed that stored (5 days; D5) but not fresh platelets (1 day; D1) cause TRALI via ceramide mediated endothelial barrier dysfunction. As biological ceramides are hydrophobic, extracellular vesicles (EVs) may be required to shuttle these sphingolipids from platelets to endothelial cells. Adding to complexity, EV formation in turn requires ceramide. We hypothesized that ceramide-dependent EV formation from stored platelets and EV-dependent sphingolipid shuttling induce TRALI. EVs formed during storage of murine platelets were enumerated, characterized for sphingolipids and applied in a murine TRALI model in vivo and for endothelial barrier assessment in vitro. D5-EVs were more abundant, had higher long chain ceramide (C16:0, C18:0, C20:0) and lower S1P content than D1-EVs. Transfusion of D5- but not D1-EVs induced characteristic signs of lung injury in vivo and endothelial barrier disruption in vitro. Inhibition or supplementation of ceramide-forming sphingomyelinase reduced or enhanced the formation of EVs, respectively, but did not alter the injuriousness per individual EV. Barrier failure was attenuated when EVs were abundant in or supplemented with S1P. Stored human platelet D4-EVs were more numerous compared with D2-EVs, contained more long chain ceramide and less S1P, and caused more EC barrier leak. Hence, platelet-derived EVs become more numerous and more injurious (more long chain ceramide, less S1P) during storage. Blockade of sphingomyelinase, EV elimination, or supplementation of S1P during platelet storage may present promising strategies for TRALI prevention.

The role of Extracellular Vesicles in Traumatic Brain Injury-induced Acute Lung Injury

2021 ◽  
Author(s):  
Chao-Nan Zhang ◽  
Fan-Jian Li ◽  
Zi-Long Zhao ◽  
Jian-Ning Zhang
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Extracellular Vesicles ◽  
Genetic Material ◽  
Peripheral Circulation ◽  
Target Cells ◽  
New Ideas ◽  
Pass Through

Acute lung injury (ALI), a common complication after traumatic brain injury (TBI), can evolve into acute respiratory distress syndrome (ARDS) and has a mortality rate of 30-40%. Secondary ALI after TBI exhibits the following typical pathological features: infiltration of neutrophils into the alveolar and interstitial space, alveolar septal thickening, alveolar edema and hemorrhage. Extracellular vesicles (EVs) were recently identified as key mediators in TBI-induced ALI. Due to their small size and lipid bilayer, they can pass through the disrupted blood-brain barrier (BBB) into the peripheral circulation and deliver their contents, such as genetic material and proteins, to target cells through processes such as fusion, receptor-mediated interactions, and uptake. Acting as messengers, EVs contribute to mediating brain-lung crosstalk after TBI. In this review, we aim to summarize the mechanism of EVs in TBI-induced ALI, which may provide new ideas for clinical treatment.

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