Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression

Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen

doi:10.1016/j.bbrc.2017.08.093

Cited by 27 publications

(22 citation statements)

References 12 publications

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“…Importantly, we demonstrated that miR-let-7i could protect cells from OGD-induced cell damage in vitro by targeting Bcl-2. Similarly, it was also reported to attenuate endothelial cell damage in the OGD model, which further supported our results (Xiang et al, 2017). Besides, multiple evidences have proved that miRNAs, such as miR-203, let-7, miR-195, and miR-122, all exert the anti-apoptotic effect to protect against cell injury (Yang et al, 2015;Guo et al, 2018;Han et al, 2018;Cheng et al, 2019).…”

Section: Discussionsupporting

confidence: 89%

“…*p < 0.05. Furthermore, Xiang et al (2017) have reported that miR-let-7i could attenuate brain microvascular endothelial cell damage by decreasing TLR4 expression in the OGD model. The above evidences suggested that the up-regulation of miR-let-7i could alleviate the neuronal damage by targeting various regulatory factors, and it has the potential as a therapeutic target for PSCI.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2

Wang

Huang

et al. 2020

Front. Neurosci.

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Background: The mechanism of post-stroke cognitive impairment (PSCI) has not been explained. We aimed to investigate whether miR-let-7i participates in the PSCI and illuminates its underlying role in oxygen-glucose deprivation (OGD)-induced cell apoptosis.Methods: Blood samples from 36 subjects with PSCI and 38 with post-stroke cognitive normality (Non-PSCI) were collected to evaluate the differential expression of miRlet-7 family members, using qRT-PCT analysis. Spearman correlation was performed to estimate the correlation between the miR-1et-7i level and Montreal Cognitive Assessment (MoCA) score. Treatment of SH-SY5Y cells with OGD was used to induce cell apoptosis in vitro. Effects of miR-let-7i on OGD-induced cell apoptosis was estimated after transfection. The target gene of miR-let-7i was analyzed by dual luciferase reporter gene assay.Results: The expression of miR-let-7i was up-regulated in PSCI patients compared with Non-PSCI (p < 0.001) and negatively correlated with MoCA score (r = −0.643, p < 0.001). When exposed to OGD, SH-SY5Y cells showed significant apoptosis accompanied by miR-let-7i up-regulation. In OGD-treated cells, miR-let-7i up-regulation was accompanied by cell apoptosis, while down-regulation showed the opposite effect. Luciferase reporter assay showed that Bcl-2 was a target gene of miR-let-7i. Western blot showed that miR-let-7i up-regulation promoted Bcl-2 expression, while qRT-PCR showed that miR-let-7i had no effect on Bcl-2 expression.Conclusion: miR-let-7i was overexpressed in PSCI patients and it could be used as a diagnostic biomarker for PSCI. We illuminated the potential mechanism that miR-let-7i alleviated OGD-induced cell damage by targeting Bcl-2 at the post-transcriptional level.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2

Wang

Huang

et al. 2020

Front. Neurosci.

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“…Indirect inhibition of TLR signaling results in the regression of tumor growth and expansion. Direct TLR-4 inhibition is induced by different miRNAs [99][100][101][102]. miRNA molecules directly develop inhibitory features, in particular during stages of TLR-4 activation.…”

Section: Mirna/tlr-4 Interplaymentioning

confidence: 99%

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives

Litak

Grochowski

Litak³

et al. 2020

IJMS

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Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.

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“…As previously reported, let‐7i represses endMT by inhibiting of TGF‐βR1 26 . Our previous research also showed that let‐7i expression decreases in oxygen‐glucose deprivation model 29 . Therefore, we aimed to determine whether or not let‐7i is involved in endMT after ischemic stroke.…”

Section: Resultsmentioning

confidence: 75%

“…However, let‐7i of ECs inhibits endMT, 26 and let‐7g improves the function of ECs 27 and protects the blood‐brain barrier (BBB) under neuroinflammatory conditions 28 . Moreover, we found that the expression of let‐7i in ECs was downregulated under oxygen‐glucose‐deprivation 29 in vitro. Therefore, we aimed to determine whether or not let‐7i in ECs participates in pathology mechanism after ischemic stroke in vivo.…”

Section: Introductionmentioning

confidence: 86%

Ischemia‐reperfusion injury of brain induces endothelial‐mesenchymal transition and vascular fibrosis via activating let‐7i/TGF‐βR1 double‐negative feedback loop

Chen

Wang

et al. 2020

FASEB j.

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Let-7i modulates the physical function and inflammation in endothelial cells (ECs).However, whether the let-7i of ECs involves in brain vasculature and ischemic stroke is unknown. Using inducible Cadherin5-Cre lineage-tracking mice, a loxp-RNAsponge conditional knockdown of let-7 in ECs-induced increase of transforming growth factor-β receptor type 1 (TGF-βR1), endothelial-mesenchymal transition (endMT), vascular fibrosis, and opening of the brain-blood barrier (BBB). By this lineage-tracking mice, we found that ECs underwent endMT after transient middle cerebral artery occlusion (MCAO). Through specifically overexpressed let-7i in ECs, we found that it reduced TGF-βR1, endMT, and vascular fibrosis. Furthermore, this overexpression reduced the infarct volume and leakage of the BBB, and improved the neurological function. Further, the expression of let-7i decreased after MCAO, but was reversed by antagonist of TGF-βR1 or inhibition of Mek phosphorylation.And the inhibition of Mek attenuated the vascular fibrosis after MCAO. In summary, we concluded that ischemic stroke activates a let-7i/TGF-βR1 double-negative feedback loop, thereby inducing endMT and vascular fibrosis. These results suggest that endMT is a potential target for the treatment of cerebral vascular fibrosis.

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Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression

Cited by 27 publications

References 12 publications

MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2

MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2

TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives

Ischemia‐reperfusion injury of brain induces endothelial‐mesenchymal transition and vascular fibrosis via activating let‐7i/TGF‐βR1 double‐negative feedback loop

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