The mechanism of rapamycin in the intervention of paraquat-induced acute lung injury in rats

Chen, Da; Jiao, Guangyu; Ma, Tao; Liu, Xiaowei; Yang, Chen; Liu, Zhi

doi:10.3109/00498254.2014.995149

Cited by 13 publications

(20 citation statements)

References 31 publications

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“…ACE2 is the homolog of ACE but counterbalances the ACE activity through induction of degradation of Ang II [5]. Recently, we and others have shown that ACE2 has therapeutic effects on ALI, at least partially through suppression of apoptosis of PECs [6][7][8][9][10]. However, the molecular mechanisms underlying the inhibitory effects of ACE2 on cell apoptosis are not completely understood.…”

Section: Introductionmentioning

confidence: 97%

“…The mouse bleomycin-ALI model has been performed as has been described before [6][7][8][9][10]14]. H&E staining of mouse lung tissue showed significant pneumonitis, inflammatory exudates, fibroblastic foci and distortion of the normal architecture of the lung after ATI, while ACE2 reduced the severity of these features (Fig.…”

Section: Ace2 Reduces Ali Features In Mouse Lungmentioning

confidence: 99%

“…After acclimatization for 1 week, a group of mice were used as the no-injury group and received no treatments (NT). The lung injury model was induced in another groups of mice, by intraperitoneal administration of the bleomycin solution (10mg/mL, Sigma-Aldrich, St Louis, MO, USA) at 20 mg/kg body weight, as has been applied and described before [6][7][8][9][10]14]. This ALI model is stable and easy to be built.…”

Section: Animal Manipulationsmentioning

confidence: 99%

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Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

Hong

Gao²,

Xie

et al. 2015

Cell Physiol Biochem

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This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Abstract Background/Aims: Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI). The effects of ACE2 in ALI have been shown to not only result from its antagonizing hydrolyzing angiotensin II (AngII), which is responsible for reduction in the vascular tension and pulmonary accumulation of inflammatory cells, but also result from a role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells (PECs). Nevertheless, the underlying mechanisms of the role of ACE2 on PEC apoptosis are not completely understood. Methods: Here, we used a bleomycin-induced mouse model for ALI that has been published in our previous studies. We analyzed the mRNA and protein levels of an anti-apoptotic protein Bcl-2 in the ALI-mice that have been treated w/o ACE2. We analyzed miR-4262 levels in the mouse lung in these mice. Bcl-2-targeting miRNAs were predicted using bioinformatics algorithms and a luciferase reporter assay was applied to examine the effects of miR-4262 on the Bcl-2 protein translation upon their binding to 3'-UTR of Bcl-2 mRNA. Adeno-associated viruses carrying either miR-4262 mimics or antisense were injected into ALI-mice without ACE2, and their effects on the apoptosis in mouse lung cells were analyzed by Western blot. Results: ACE2 inhibited the ALI-induced apoptosis of pulmonary cells in vivo partially through upregulation of Bcl-2 protein, but not Bcl-2 mRNA. ACE2 appeared to significantly suppress the upregulation of miR-4262 in mouse lung after ALI. MiR-4262 was found to target 3'-UTR of Bcl-2 mRNA to inhibit its protein translation in PECs. In vivo administration of antisense of miR-4262 decreased apoptosis of pulmonary cells and severity of the ALI in mice. Conclusion: ACE2-induced suppression of miR-4262 partially contribute to the inhibition of the PEC apoptosis after ALI through Bcl-2. MiR-4262 may be a novel promising treatment target for ALI and ARDS.

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Section: Introductionmentioning

confidence: 97%

Section: Ace2 Reduces Ali Features In Mouse Lungmentioning

confidence: 99%

Section: Animal Manipulationsmentioning

confidence: 99%

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Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

Hong

Gao²,

Xie

et al. 2015

Cell Physiol Biochem

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show abstract

“…After acclimatization for 1 week, totally 10 mice were used as the no-injury group and received no treatments. The lung injury model was induced in another 20 mice, by intraperitoneal administration of the bleomycin solution (10mg/ mL, Sigma-Aldrich, St Louis, MO, USA) at 20 mg/kg body weight, as has been applied and described before [9][10][11][12][13][14][15]. This ALI model is stable and easy to be built.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

“…ACE2 is the homolog of ACE but counterbalances the ACE activity through induction of degradation of Ang II into the vasodilator peptide Ang 1-7, which counteracts the effects of Ang II after binding to Mas receptor [8]. Recently, we and others have shown that ACE2 has therapeutic effects on ALI, especially when ACE2 is applied together with transplantation of human umbilical cord mesenchymal stem cells (uMSCs) [9][10][11][12][13][14][15]. However, the underlying mechanisms remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing SMAD2 Phosphorylation

Gao²,

Sun

et al. 2015

Cell Physiol Biochem

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Background/Aims: Angiotensin converting enzyme 2 (ACE2) has an established role in suppressing the severity of acute lung injury (ALI), especially when it was applied together with transplantation of human umbilical cord mesenchymal stem cells (uMSCs). Although the effects of ACE2 in ALI are believed to mainly result from its role in hydrolyzing angiotensin II (AngII), which subsequently reduces the vascular tension and subsequent pulmonary accumulation of inflammatory cells, we and others have recently reported a possible role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells. However, the underlying mechanisms remain undetermined. Methods: Here, we analyzed the alteration in lung injury severity in ALI after ACE2, by histology and inflammatory cytokine levels. We analyzed apoptosis-associated proteins in lung after ALI, as well as in cultured endothelial cells treated with nitric oxide (NO). We overexpressed SMAD7 to inhibit SMAD2 signaling in cultured endothelial cells and examined its effects on NO-induced cell apoptosis. Results: ACE2 alleviated severity of lung injury after ALI. ACE2 significantly decreased the ALI-induced apoptosis of pulmonary cells in vivo, and ACE2 protected endothelial cells against NO-induced apoptosis in vitro. NO induced phosphorylation of a key factor of transforming growth factor β (TGF β) receptor signaling, SMAD2, which could be dose-dependently inhibited by ACE2. Inhibition of SMAD2 phosphorylation through expression of its inhibitor SMAD7 significantly inhibited NO-induced cell apoptosis, without need for ACE2. Conclusion: Our data suggest that ACE2-mediated AngII degradation may inhibit AngII-mediated SMAD2-phophorylation, possibly through a TGFβ-independent manner, which subsequently suppresses the ALI-induced cell death. Our results thus reveal a novel molecular pathway that controls the pathogenesis of ALI.

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Embelin impact on paraquat‐induced lung injury through suppressing oxidative stress, inflammatory cascade, and MAPK/NF‐κB signaling pathway

Sreeharsha

2020

J Biochem & Molecular Tox

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The current examination was intended to observe the defensive impacts of embelin against paraquat‐incited lung damage in relationship with its antioxidant and anti‐inflammatory action. Oxidative stress marker, like malondialdehyde (MDA), antioxidative enzymes, for example, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH Px), inflammatory cytokines, such as interleukin‐1β (IL‐1β), tumor necrosis factor‐α, and IL‐6, histological examination, and nuclear factor kappa B/mitogen‐activated protein kinase (NF‐κB/MAPK) gene expression were evaluated in lung tissue. Embelin treatment significantly decreased MDA and increased SOD, CAT, and GSH Px. Embelin significantly reduced levels of inflammatory cytokines in paraquat‐administered and paraquat‐intoxicated rats. In addition, embelin suggestively decreased relative protein expression of nuclear NF‐κB p65, p‐NF‐κBp65, p38 MAPK, and p‐p38 MAPKs in paraquat‐intoxicated rats. The outcomes show the impact of embelin inhibitory action on NF‐κB and MAPK and inflammatory cytokines release, and the decrease of lung tissue damage caused by paraquat.

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The mechanism of rapamycin in the intervention of paraquat-induced acute lung injury in rats

Cited by 13 publications

References 31 publications

Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing SMAD2 Phosphorylation

Embelin impact on paraquat‐induced lung injury through suppressing oxidative stress, inflammatory cascade, and MAPK/NF‐κB signaling pathway

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