MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome

Lu, Qianying; Yu, Sifan; Meng, Xiangyan; Shi, Mingyu; Huang, Siyu; Li, Junfeng; Zhang, Jianfeng; Liang, Yangfan; Ji, Mengjun; Zhao, Yanmei; Fan, Haojun

doi:10.3390/ijms23105545

Cited by 26 publications

(17 citation statements)

References 136 publications

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“…microRNAs (miRNAs) represent a group of small noncoding RNA and have the ability to modulate gene expression via targeting mRNA for early degradation or inhibition of its translation. In light of miRNA control of in ammatory-immune responses and cell-cell interactions from previous evidence [8], miRNAs are reported to be involved in the pathological processes of various lung diseases, including ALI [9]. Dysregulation of miR-29 family occurs in several human cancers, such as breast cancer [10], osteosarcoma [11], and bladder urothelial cancer [12].…”

Section: Introductionmentioning

confidence: 98%

Inhibition of miR-29b-1-5p Attenuates Inflammatory Response and Pulmonary Fibrosis in LPS-Induced Acute Lung Injury by Regulating RTN4 Expression

Wang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Acute lung injury (ALI) is a severe respiratory disorder causing alveolar-capillary barrier, leading to a high rate of morbidity and death in critically ill individuals. microRNAs (miRNAs)-mediated mechanism in the pathogenesis of ALI has attracted much interest. Herein, we attempt to characterize a candidate miRNA and its downstream target that is linked to the pathogenesis of ALI. Methods. LPS-conditioned MH-S cells were treated with miR-29a-1-5p mimic, inhibitor, and RNT4 expression vector, and the ALI animal model was injected with agomir and antagomir of miR-29b-1-5p and RNT4 expression vector, in which the pro-inflammatory cytokine production, cell viability and apoptosis, myeloperoxidase (MPO) activity, wet/dry (W/D) ratio, and expression of TGF-β1, α-smooth muscle actin (α-SMA), E-cadherin, and vimentin were examined. miR-29a-1-5p inhibition of RTN4 translation was confirmed by luciferase activity assays. Results. An elevated miR-29a-1-5p expression was demonstrated in LPS-conditioned MH-S cells. miR-29a-1-5p inhibitor transfection attenuated the production of pro-inflammatory cytokines and MH-S cell viability but enhanced the apoptosis. miR-29a-1-5p inhibition of RTN4 translation was demonstrated in the setting of LPS-induced ALI. LPS-induced murine models demonstrated upregulated miR-29a-1-5p. Intravenous injection of miR-29b-1-5p agomir attenuated mouse lung injury and pulmonary fibrosis. RTN4 overexpression resisting to miR-29a-1-5p overexpression was demonstrated in LPS-induced murine models. Conclusion. The findings obtained from the study that disturbing the action of miR-29a-1-5p may be a novel therapeutic strategy for preventing ALI.

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Section: Introductionmentioning

confidence: 98%

Inhibition of miR-29b-1-5p Attenuates Inflammatory Response and Pulmonary Fibrosis in LPS-Induced Acute Lung Injury by Regulating RTN4 Expression

Wang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…With the progress of research, several inflammation-related mechanisms in ALI have been discovered. In addition to the TLRs mediate NF-κB signaling pathway involved in our study, there are also JAK2/STAT3, NLRP3 inflammasome, PI3K/AKT, p38 MAPK and so on [ 58 ]. Whether there are other miR-146a-5p related pathways or other components involved in the hucMSC-EV-induced improvement in ALI caused by SM remains to be further studied because the components of extracellular vesicles are very diverse, and the injury mechanism of SM is complicated and has not been clearly elaborated.…”

Section: Discussionmentioning

confidence: 99%

MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury

Pei¹,

Cen²,

Zhang³

et al. 2023

Stem Cell Res Ther

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Background Sulfur mustard (SM) is a highly toxic chemical warfare agent that has caused numerous casualties during wars and conflicts in the past century. Specific antidotes or therapeutic strategies are rare due to the complicated mechanism of toxicity, which still awaits elucidation. Clinical data show that acute lung injury (ALI) is responsible for most mortality and morbidity after SM exposure. Extracellular vesicles are natural materials that participate in intercellular communication by delivering various substances and can be modified. In this study, we aim to show that extracellular vesicles derived from human umbilical cord mesenchymal stromal cells (hucMSC-EVs) could exert therapeutic effects on SM-induced ALI, and to explain the underlying mechanism of effects. Methods MiR-146a-5p contained in hucMSC-EVs may be involved in the process of hucMSC-EVs modulating the inflammatory response to SM-induced ALI. We utilized miR-146a-5p delivered by extracellular vesicles and further modified hucMSCs with a miR-146a-5p mimic or inhibitor to collect miR-146a-5p-overexpressing extracellular vesicles (miR-146a-5p+-EVs) or miR-146a-5p-underexpressing extracellular vesicles (miR-146a-5p−-EVs), respectively. Through in vivo and in vitro experiments, we investigated the mechanism. Results The effect of miR-146a-5p+-EVs on improving the inflammatory reaction tied to SM injury was better than that of hucMSC-EVs. We demonstrated that miR-146a-5p delivered by hucMSC-EVs targeted TRAF6 to negatively regulate inflammation in SM-induced ALI models in vitro and in vivo. Conclusion In summary, miR-146a-5p delivered by hucMSC-EVs targeted TRAF6, causing hucMSC-EVs to exert anti-inflammatory effects in SM-induced ALI; thus, hucMSC-EVs treatment may be a promising clinical therapeutic after SM exposure. Graphical Abstract

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“…In addition, miRNAs that play a major regulatory role are present at low levels in native EVs, therefore they cannot effectively exert therapeutic effects. [28] To solve these problems and improve therapeutic efficiency, we modified EC-EVs to establish eEVs. miRNAs are small non-coding RNAs.…”

Section: Discussionmentioning

confidence: 99%

Endothelium‐Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury

Gu,

Sun,

Liu

et al. 2023

Advanced Science

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Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment. Extracellular vesicles (EVs) are promising nanotherapeutic agents against ALI. Herein, endothelium‐derived engineered extracellular vesicles (eEVs) that deliver microRNA‐125b‐5p (miRNA‐125b) to lung tissues exerting a protective effect on endothelial barrier integrity are reported. eEVs that are modified with lung microvascular endothelial cell‐targeting peptides (LET) exhibit a prolonged retention time in lung tissues and targeted lung microvascular endothelial cells in vivo and in vitro. To improve the efficacy of the EVs, miRNA‐125b is loaded into EVs. Finally, LET‐EVs‐miRNA‐125b is constructed. The results show that compared to the EVs, miRNA‐125b, and EVs‐miRNA‐125b, LET‐EVs‐miRNA‐125b exhibit the most significant treatment efficacy in ALI. Moreover, LET‐EVs‐miRNA‐125b is found to have an important protective effect on endothelial barrier integrity by inhibiting cell apoptosis, promoting angiogenesis, and protecting intercellular junctions. Sequencing analysis reveals that LET‐EVs‐miRNA‐125b downregulates early growth response‐1 (EGR1) levels, which may be a potential mechanism of action. Taken together, these findings suggest that LET‐EVs‐miRNA‐125b can treat ALI by protecting the endothelial barrier integrity.

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MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome

Cited by 26 publications

References 136 publications

Inhibition of miR-29b-1-5p Attenuates Inflammatory Response and Pulmonary Fibrosis in LPS-Induced Acute Lung Injury by Regulating RTN4 Expression

Inhibition of miR-29b-1-5p Attenuates Inflammatory Response and Pulmonary Fibrosis in LPS-Induced Acute Lung Injury by Regulating RTN4 Expression

MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury

Endothelium‐Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury

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