LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4

Wang, Hongwei; Zheng, Xiaoxiao; Jin, Jing; Zheng, Lirong; Guan, Ting; Huo, Yangfan; Xie, Shufen; Wu, Ying; Chen, Wei

doi:10.1186/s12929-020-00635-0

Cited by 106 publications

(67 citation statements)

References 49 publications

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“…As it was determined that MALAT1 can act as ceRNA for miR-145, MALAT1 positively regulated AQP4 via miR-145 downregulation. Altogether, the study validated that MALAT1 silencing protects against cerebral I/ R injury by regulating the miR-145/AQP4 axis [3].…”

Section: Lncrna Malat1supporting

confidence: 59%

Long Non-coding RNAs as Promising Therapeutic Approach in Ischemic Stroke: a Comprehensive Review

et al. 2020

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In recent years, ischemic stroke (IS) has been one of the major causes of disability and mortality worldwide. The general mechanism of IS is based on reduced blood supply to neuronal tissue, resulting in neuronal cell damage by various pathological reactions. One of the main techniques for acute IS treatment entails advanced surgical approaches for restoration of cerebral blood supply but this is often associated with secondary brain injury, also known as ischemic reperfusion injury (I/R injury). Many researches have come to emphasize the significant role of long non-coding RNAs (lncRNAs) in IS, especially in I/R injury and their potential as therapeutic approaches. LncRNAs are non-protein transcripts that are able to regulate cellular processes and gene expression. Further, lncRNAs have been shown to be involved in neuronal signaling pathways. Several lncRNAs are recognized as key factors in the physiological and pathological processes of IS. In this review, we discuss the role of lncRNAs in neuronal injury mechanisms and their association with brain neuroprotection. Moreover, we identify the lncRNAs that show the greatest potential as novel therapeutic approaches in IS, which therefore merit further investigation in preclinical research.

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Section: Lncrna Malat1supporting

confidence: 59%

Long Non-coding RNAs as Promising Therapeutic Approach in Ischemic Stroke: a Comprehensive Review

et al. 2020

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“…The blood occlusion was administrated for 2 h, then the blood supplement was restored for 24 h. The mice of the sham group received a similar operation with no MCAO/R occlusion. The mice were intracerebroventricularly injected with control shRNA or circTTC3 shRNA (before MCAO/R occlusion) as in the previous reports [ 25 , 26 ]. Then, the mice succumbed to death, and the brain tissues were obtained for further analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The primary astrocytes were isolated from the cerebellum from C57BL/6J mice and cultured in DMEM medium (Gibco, USA) with 10% FBS (Gibco, USA) at the condition of 5% CO 2 and 37 °C as described previously [ 26 ]. The levels of TNF-α and IL-1β were analyzed by ELISA kits (Sangon Biotech, China).…”

Section: Methodsmentioning

confidence: 99%

Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction

Yang

Zang

Cui³

et al. 2021

Stem Cell Res Ther

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Background Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. Methods The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. Results Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and β-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. Conclusion Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.

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“…The brain tissues were cut into 2-mm coronal sections and then stained in 2% 2,3,5-triphenyltetrazolium chloride (TTC) (17779, Sigma-Aldrich, United States). The infarct volume was detected and analyzed by a blinded observer using ImageJ v1.37 (NIH, Bethesda, MA, United States) as described previously [ 53 ] and normalized and is presented as a percentage of the volume in the nonischemic hemisphere to correct for edema.…”

Section: Methodsmentioning

confidence: 99%

Coicis semen protects against focal cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting angiogenesis via the TGFβ/ALK1/Smad1/5 signaling pathway

Yin

et al. 2020

Aging

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Background: Ischemic stroke is a devastating disease that causes long-term disability. However, its pathogenesis is unclear, and treatments for ischemic stroke are limited. Recent studies indicate that oxidative stress is involved in the pathological progression of ischemic stroke and that angiogenesis participates in recovery from ischemic stroke. Furthermore, previous studies have shown that Coicis Semen has antioxidative and anti-inflammatory effects in a variety of diseases. In the present study, we investigated whether Coicis Semen has a protective effect against ischemic stroke and the mechanism of this protective effect. Results: Coicis Semen administration significantly decreased the infarct volume and mortality and alleviated neurological deficits at 3, 7 and 14 days after MCAO. In addition, cerebral edema at 3 days poststroke was ameliorated by Coicis Semen treatment. DHE staining showed that ROS levels in the vehicle group were increased at 3 days after reperfusion and then gradually declined, but Coicis Semen treatment reduced ROS levels. The levels of GSH and SOD in the brain were increased by Coicis Semen treatment, while MDA levels were reduced. Furthermore, Coicis Semen treatment decreased the extravasation of EB dye in MCAO mouse brains and elevated expression of the tight junction proteins ZO-1 and Occludin. Double immunofluorescence staining and western blot analysis showed that the expression of angiogenesis markers and TGFβ pathway-related proteins was increased by Coicis Semen administration. Consistent with the in vivo results , cytotoxicity assays showed that Coicis Semen substantially promoted HUVEC survival following OGD/RX in vitro . Additionally, though LY2109761 inhibited the activation of TGFβ signaling in OGD/RX model animals, Coicis Semen cotreatment markedly reversed the downregulation of TGFβ pathway-related proteins and increased VEGF levels. Methods: Adult male wild-type C57BL/6J mice were used to develop a middle cerebral artery occlusion (MCAO) stroke model. Infarct size, neurological deficits and behavior were evaluated on days 3, 7 and 14 after staining. In addition, changes in superoxide dismutase (SOD), GSH and malondialdehyde (MDA) levels were detected with a commercial kit. Blood-brain barrier (BBB) permeability was assessed with Evans blue (EB) dye. Western blotting was also performed to measure the levels of tight junction proteins of the BBB. Additionally, ELISA was performed to measure the level of VEGF in the brain. The colocalization of CD31, angiogenesis markers, and Smad1/5 was assessed by double immunofluorescent staining. TGFβ pathway-related proteins were measured by western blotting. Furthermore, the cell viability of human umbilical vein endothelial cells (HUVECs) following oxygen-glucose deprivation/reoxygenation (OGD/RX) was measured by Cell Counting Kit (CCK)-8 assay. Conclusions: Coicis Semen treatment alleviates brain damage induced by ischemic stroke through inhibitin...

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LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4

Cited by 106 publications

References 49 publications

Long Non-coding RNAs as Promising Therapeutic Approach in Ischemic Stroke: a Comprehensive Review

Long Non-coding RNAs as Promising Therapeutic Approach in Ischemic Stroke: a Comprehensive Review

Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction

Coicis semen protects against focal cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting angiogenesis via the TGFβ/ALK1/Smad1/5 signaling pathway

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