Potential therapeutic roles of stem cells in ischemia-reperfusion injury

Barzegar, Mansoureh; Kaur, Gaganpreet; Gavins, Felicity N. E.; Wang, Y.; Boyer, Christen J.

doi:10.1016/j.scr.2019.101421

Cited by 53 publications

(48 citation statements)

References 243 publications

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“…1 IRI is characterized by the initial occlusion of blood flow accompanied by a restoration, occurring in stroke, myocardial IRI, renal IRI, and liver IRI, and has been ascribed to be a major cause of disability and mortality. 2 Myocardial ischemia-reperfusion injury (MIRI) has been extensively associated with boosted oxidative stress, cardiomyocyte death and mitochondrial dysfunction. 3 Furthermore, recent evidence has also suggested that responses of myocardial tissue to I/R can be modulated to impede the induced damage, which has stimulated a subject of active investigation into the underlying mechanisms of cardioprotection.…”

Section: Introductionmentioning

confidence: 99%

LncRNA TUG1 competitively binds to miR‐340 to accelerate myocardial ischemia‐reperfusion injury

Liu

et al. 2020

FASEB j.

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The aberrant expression of long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been previously associated with myocardial ischemia-reperfusion injury (MIRI), but the underlying molecular mechanisms remain elusive. The current study aimed to clarify the functional role of TUG1/microRNA (miR)-340/histone deacetylase 4 (HDAC4)/β-catenin/glucose transporter type 1 (GLUT1) axes in MIRI. The database-based analyses performed predicted the downstream factors of lncRNA TUG1. In the MIRI mouse models and hypoxia/reoxygenation (H/R)-induced cardiomyocyte models, the expression of TUG1/miR-340/HDAC4/β-catenin/GLUT1 was manipulated to examine their effects on the infarction area, cardiomyocyte viability and apoptosis employing the Evans blue/TTC double staining, CCK-8 and TUNEL assays. Furthermore, the dual luciferase reporter and RIP assays verified the binding affinity of miR-340 to TUG1 and HDAC4. Subsequently, a negative correlation between miR-340 and TUG1 or HDAC4 expression was identified in myocardial tissues of MIRI mice and H/R-induced cardiomyocyte models, along with a positive correlation between TUG1 and HDAC4. Additionally, it was established that TUG1 bound to miR-340, and miR-340 targeted HDAC4. TUG1 upregulated HDAC4 expression, thereby promoting MIRI in the mouse models. HDAC4 was proven to repress the expression of β-catenin and its target gene GLUT1. Moreover, the in vivo experiments validated that the inhibition of TUG1/miR-340/HDAC4/β-catenin/ GLUT1 axes alleviated MIRI in mice. Collectively, the current study uncovered the role of TUG1/miR-340/HDAC4/β-catenin/GLUT1 axes in MIRI mouse models and H/R-induced cardiomyocyte models which may be a potential therapeutic target for MIRI treatment.

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Section: Introductionmentioning

confidence: 99%

LncRNA TUG1 competitively binds to miR‐340 to accelerate myocardial ischemia‐reperfusion injury

Liu

et al. 2020

FASEB j.

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“…Ischemia-reperfusion injury (I/RI), produced by an initial interruption of organ blood flow and its subsequent restoration, contributes significantly to the pathophysiologies of stroke [22]. The ischemic stroke model induced by the middle cerebral artery occlusion and reperfusion (MCAO/R) has proven to be one of the most logical and effective animal stroke models [23].…”

Section: Discussionmentioning

confidence: 99%

Analgecine inhibits NF-kB to regulate microglia polarization by TLR4 MyD88-dependent and MyD88-independent pathways in ischemic stroke

Gong

Chen

Wang

et al. 2020

Preprint

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Background: Microglia polarization plays an important role in poststroke recovery. Inhibition of proinflammatory (M1) polarization and promotion of anti-inflammatory (M2) polarization of microglia are potential therapeutic strategies for inflammation reduction and neuronal recovery after stroke. Analgecine (AGC), the extracts of Vaccin a variola-inoculated rabbit skin, is used to treat patients with chronic low back pain due to degenerative vertebral disorders. Here, we evaluated the neuroprotective effect of AGC in stroke and investigate anti-inflammatory mechanism of AGC on microglia-mediated neural damage.Methods: Sprague-Dawley (SD) rats underwent 120 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. We injected AGC intravenously into rats starting 3 h after the onset of MCAO. Then we investigated the effect of AGC on neurological impairment, neuronal loss and inflammatory cytokines. For in vitro study, we examined the effect of AGC on microglial polarization in oxygen-glucose deprivation/reperfusion (OGD/R) or LPS/IFN-γ induced microglia cells and further investigated neuroprotective effect of ACG in microglia-mediated neural damage based on the direct or indirect co-culture systems. Finally, TLR4/Myd88/ NF-κB pathway was detected in OGD/R-induced microglia cells with or without Myd88 siRNA transfection.Results: AGC treatment reduced the neurological deficits and suppressed neuronal loss. In terms of inflammatory cytokines, AGC inhibited the release of pro-inflammatory cytokines and elevated the content of anti-inflammatory cytokines in vivo (SD rats) and in vitro (microglia). We further showed that AGC promoted M1 to M2 phenotypic transition of microglia in OGD/R or LPS/IFN-γ induced microglia cells. Based on the direct or indirect co-culture systems, we found AGC indirectly inhibits LPS/IFN-γ-induced neuronal damage by modulating microglial polarization. Moreover, AGC suppressed the nuclear translocation of the phosphorylation of NF-κB p65 by inhibiting the TLR4/Myd88/TRAF6 but not TLR9 signaling. We also confirmed that AGC-regulated TLR4 inhibition partly dependent on Myd88 in a Myd88 depletion cell line.Conclusion: Our findings provide a new understanding of AGC in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing TLR4 MyD88-dependent and MyD88-independent pathways. Thus, AGC treatment may represent a novel approach in inflammation reduction or poststroke recovery.

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“…The analysis of neural stem cells' secretome showed that they secrete different growth factors, hESC-NPCs GFP after brain ischemia/ reperfusion Leila Arab et al e.g., VEGF, glial cell-derived neurotrophic factor (GDNF), triiodothyronine, NGF, and fibroblast growth factor 8 (FGF8), etc. 28,[32][33][34][35][36] In our previous studies, the regulation of upstream genes (NLRP1, NLRP3, ASC, and caspase-1) and downstream genes (TNF-α, IL-1β, IL-18, and IL-6) of inflammasome complex has been investigated. These studies demonstrated that transplanted stem cells from different sources from human can reduce the inflammation by inhibit the formation and also action of inflammasome complexes and consequently prevent the secondary injury in nervous system.…”

Section: Discussionmentioning

confidence: 99%

Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210

Arab

Fanni

Nemati

et al. 2020

J. Contemp. Med. Sci.

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Objective: In this study, we evaluated the effects of human embryonic derived neural progenitor cells on neurological score, histopathological changes, and miRNA-210 as biomarkers of regeneration. Methods: The animals were randomly divided into the four groups: Sh (sham), MCAO (middle cerebral artery occlusion), MCAO+PBS, MCAO+Cell. One day after MCAO induction, embryonic derived neural progenitor cells (hESC-NPCsGFP) or PBS were injected intracerebroventriculary in MCAO+Cell or MCAO+PBS groups. On day 1, 2, 3, and 7 after ischemia induction, the neurological score was tested in each rat. At 48h, the expression of miRNA-210 was evaluated and 7 days after, the pathological assessments were performed by H&E staining. Results: Neurological score showed the promotion of functional recovery in MCAO+Cell group. Based on H&E staining, the percentage of neural death in ischemic region reduced in MCAO+Cell group. The miRNA-210 significantly upregulated in both brain and blood samples. Conclusion: According to the findings, hESC-NPCsGFP injection could up-regulate the miRNA-210 of tissue and blood to support the neuroprotective and regenerative effect of hESC-NPCsGFP in the ischemic lesion and improved the neurological score and reduce the neural death in ischemic region.

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Potential therapeutic roles of stem cells in ischemia-reperfusion injury

Cited by 53 publications

References 243 publications

LncRNA TUG1 competitively binds to miR‐340 to accelerate myocardial ischemia‐reperfusion injury

LncRNA TUG1 competitively binds to miR‐340 to accelerate myocardial ischemia‐reperfusion injury

Analgecine inhibits NF-kB to regulate microglia polarization by TLR4 MyD88-dependent and MyD88-independent pathways in ischemic stroke

Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210

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