MiR-802 alleviates lipopolysaccharide-induced acute lung injury by targeting Peli2

You, Qinghai; Wang, Jinmei; Jia, Di; Jiang, Lijuan; Chang, Yuanmin; Li, Wenmei

doi:10.1007/s00011-019-01295-z

Cited by 21 publications

(13 citation statements)

References 25 publications

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“…Previous studies have verified that PELI2 plays a role in lung injury caused by sepsis [ 44 ], which mechanism might be related to PELI2 activation. In our study, PELI2 was predicted to be a direct downstream target of Mir-128-3P, which is associated with apoptosis and oxidative stress.…”

Section: Discussionmentioning

confidence: 96%

“…PELI2, a positive regulator in LPS/TLR4 pathway, has been suggested to play a role in IL-1/LPS-induced activation of ERK and JNK MAPK pathways and increased stabilization of mRNAs encoding pro-inflammatory proteins [ 29 , 30 ]. You et al found that PELI2 was upregulated in acute respiratory distress syndrome model, and miR-802 carried a protective role against LPS-induced ALI by downregulating PELI2 [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

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miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12

et al. 2021

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Objective Acute lung injury (ALI) caused by sepsis is clinically a syndrome, which is featured by damage to the alveolar epithelium and endothelium. In this study, we employed mice models of cecal ligation and puncture (CLP) and primary mice pulmonary microvascular endothelial cells (MPVECs) in vitro to investigate the effect of miR-128-3p in ALI caused by sepsis. Methods miR-128-3p agomir or randomized control were injected into adult male C57BL/6 mice 1 week before the CLP surgery. We used miR-128-3p agomir or scrambled control to transfect MPVECs and then employed lipopolysaccharide (LPS) stimulation on the cells. Pellino homolog 2 (PELI2) was predicted to be a direct target of miR-128-3p via luciferase reporter assay. MPVECs were cotransfected with lentiviral vector that expressed PELI2 (or empty vector) as well as miR-128-3p-mimics 1 day before LPS stimulation in rescue experiment. Transcriptional activity of caspase-3, cell apoptosis rate, and the expression levels of miR-128-3p, interleukin-1β (IL-1β), interleukin-6 (IL-6), and PELI2 were analyzed. Results Compared with the sham group, the lung of mice in the CLP group showed pulmonary morphological abnormalities, and the expression of IL-6 and IL-1β, caspase-3 activity, and apoptosis rate were significantly upregulated in the CLP group. Inflammatory factor levels and apoptosis rate were also significantly induced by LPS stimulation on MPVECs. Upregulation of miR-128-3p effectively inhibited sepsis-induced ALI, apoptosis as well as inflammation. miR-128-3p also played a role in antiapoptosis and anti-inflammation in MPVECs with LPS treatment. PEL12 upregulation in MPVECs alleviated miR-128-3p-induced caspase-3 activity inhibition and pro-inflammatory factor production. Conclusions miR-128-3p enabled to alleviate sepsis-induced ALI by inhibiting PEL12 expression, indicating a novel treatment strategy of miR-128-3p for sepsis-induced ALI.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12

et al. 2021

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“…MiR-802 possesses multiple functions. It has been reported to regulate cancer development, alleviate lipopolysaccharide-induced acute lung injury, and modulate the expression of human angiotensin II type I receptor (27)(28)(29). In terms of metabolism, miR-802 impairs glucose metabolism and causes nephropathy in both mice and humans with obesity (30,31).…”

Section: Discussionmentioning

confidence: 99%

Hypertrophic Adipocyte–Derived Exosomal miR‐802‐5p Contributes to Insulin Resistance in Cardiac Myocytes Through Targeting HSP60

Wen

et al. 2020

Obesity

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Objective This study aimed to elucidate the mechanism by which hypertrophic adipocytes regulate insulin signaling in cardiac myocytes. Methods Palmitate was used to induce hypertrophic 3T3‐L1 adipocytes. Exosomes were purified from normal control or hypertrophic 3T3‐L1 adipocyte‐associated conditioned medium. Exosome‐exposed neonatal rat ventricular myocytes were stimulated with insulin to investigate the effects of exosomes on insulin signaling. Small interfering RNA techniques were used to downregulate protein levels, and their efficiency was evaluated by Western blot. Results Hypertrophic adipocyte–derived exosomes highly expressed miR‐802‐5p. Insulin sensitivity of neonatal rat ventricular myocytes was negatively regulated by miR‐802‐5p. TargetScan and luciferase reporter assays revealed that heat shock protein 60 (HSP60) was a direct target of miR‐802‐5p. HSP60 silencing was found to induce insulin resistance and to mitigate the insulin‐sensitizing effects of adiponectin. In addition, HSP60 depletion significantly increased the expression levels of C/EBP‐homologous protein and enhanced oxidative stress, accompanied by the increases in the phosphorylation of JNK and IRS‐1 Ser307. Moreover, the effects of HSP60 knockdown on C/EBP‐homologous protein and oxidative stress were abolished by the inhibition of either miR‐802‐5p or endocytosis. Conclusions Hypertrophic adipocyte–derived exosomal miR‐802‐5p caused cardiac insulin resistance through downregulating HSP60. These findings provide a novel mechanism by which epicardial adipose tissue impairs cardiac function.

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“…Recent studies have reported that miRNAs, as gene expression switches, have an important role in the progression of ALI (18,19). A recent study has indicated that miR-802 was expressed at a low level in LPS-induced ALI and alleviated LPS-induced ALI by targeting Peli2 (20). Another recent study has revealed that miR-539-5p was underexpressed in sepsis-induced ALI and could protect mice from ALI (21).…”

Section: Discussionmentioning

confidence: 99%

miR‑26a‑5p alleviates lipopolysaccharide‑induced acute lung injury by targeting the connective tissue growth factor

Yang

Fei

2020

Mol Med Rep

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The aim of the present study was to investigate the regulatory functions of microRNA (miR)-26a-5p on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its molecular mechanisms. The role of miR-26a-5p on an ALI mouse model was evaluated by examining the histological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) expression levels in lung tissues and the survival of ALI mice. Moreover, the protein concentration and the number of neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) was analyzed. To explore the effect of miR-26a-5p on inflammatory responses and apoptosis, the expression levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 and apoptosis were measured by ELISA, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling staining and flow cytometry in BALF, A549 cells and lung tissues. B-cell lymphoma-2 (Bcl-2), Bax and cleaved caspase-3 in lung tissues were measured by western blotting and reverse transcription-quantitative PCR. Connective tissue growth factor (CTGF) was predicted as a direct target of miR-26a-5p using dual luciferase reporter assay. The present study sought to determine whether CTGF overexpression reversed the effect of miR-26a-5p on apoptosis and inflammatory responses in LPS-induced A549 cells. The data revealed that miR-26a-5p overexpression ameliorated LPS-induced ALI, which was implicated by fewer histopathological changes, W/D ratio, apoptosis in lung tissues and the survival of ALI mice. Moreover, miR-26a-5p overexpression alleviated LPS-induced inflammatory responses in ALI mice via the reduction of total protein, neutrophil and lymphocyte counts and the expression levels of TNF-α, IL-1β, IL-6, MDA and MPO activity in BALF. Similarly, miR-26a-5p overexpression decreased apoptosis and the expression of TNF-α, IL-1β and IL-6 in LPS-induced A549 cells. CTGF was a direct target of miR-26a-5p. CTGF overexpression reversed the effect of miR-26a-5p on cell apoptosis and inflammatory responses in LPS-induced A549 cells. The present study demonstrated that miR-26a-5p could attenuate lung inflammation and apoptosis in LPS-induced ALI by targeting CTGF.

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MiR-802 alleviates lipopolysaccharide-induced acute lung injury by targeting Peli2

Cited by 21 publications

References 25 publications

miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12

miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12

Hypertrophic Adipocyte–Derived Exosomal miR‐802‐5p Contributes to Insulin Resistance in Cardiac Myocytes Through Targeting HSP60

miR‑26a‑5p alleviates lipopolysaccharide‑induced acute lung injury by targeting the connective tissue growth factor

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