Roles of the miR-137-3p/CAPN-2 gene pair in ischemia-reperfusion-induced neuronal apoptosis through modulation of p35 cleavage and subsequent caspase-8 overactivation

2019 ◽  
Author(s):  
He Wang ◽  
Qian Yu ◽  
Zai-Li Zhang ◽  
Hong Ma ◽  
Xiao-Qian Li
Keyword(s):  
Motor Function ◽  
Gene Pair ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Motor Dysfunction ◽  
Luciferase Assay ◽  
Caspase 8 ◽  
Intracellular Ca ◽  
Expression And Activity

Abstract Background: Neuron survival after ischemia-reperfusion (IR) injury is the primary determinant of motor function prognosis. MicroRNA (miR)-based gene therapy has gained attention. Our previous work explored the mechanisms by which miR-137-3p modulates neuronal apoptosis in both in vivo and in vitro IR models.Methods: IR-induced motor dysfunction and spinal calpain (CAPN) subtype expression and subcellular distribution were detected within 12 h post IR. Dysregulated miRs, including miR-137-3p, were identified by miR microarray analysis and confirmed by PCR. Luciferase assay confirmed that CAPN-2 is a corresponding target of miR-137-3p, and their modulation of motor function was evaluated by intrathecal infection with synthetic miRs. CAPN-2 activity was measured by the intracellular Ca2+ concentration and mean fluorescence intensity in vitro. Neuronal apoptosis was detected by flow cytometry and lactate dehydrogenase (LDH) release. The activities of p35, p25, Cdk5 and caspase-8 were evaluated by ELISA and Western blotting after transfection with specific inhibitors and miRs.Results: The IR-induced motor dysfunction time course was closely associated with CAPN-2 protein upregulation, which was mainly distributed in neurons. The miR-137-3p/CAPN-2 gene pair was confirmed by luciferase assay. miR-137-3p mimic significantly improved IR-induced motor dysfunction and decreased CAPN-2 expression, even in combination with recombinant rat calpain-2 (rr-CALP2) injection, whereas miR-137-3p inhibitor reversed these effects. Similar changes were observed in the intracellular Ca2+ concentration and CAPN-2 expression and activity when cells were exposed to OGD/R and transfected with synthetic miRs in vitro. Moreover, double fluorescence revealed that CAPN-2, p35, p25 and caspase-8 were all identically distributed in neurons. The decrease in CAPN-2 expression and activity was accompanied by the opposite changes in p35 activity and protein expression in cells transfected with miR-137-3p mimic, roscovitine (a Cdk5 inhibitor) or Z-IETD-FMK (a caspase-8 inhibitor). Correspondingly, more surviving neurons were observed with the abovementioned treatments, indicated by a decrease in apoptotic cell percentage, LDH release and p25, Cdk5, caspase-8 and caspase-3 protein expression.Conclusions: The miR-137-3p/CAPN-2 gene pair functions to modulate neuronal apoptosis during IR injury, possibly through CAPN-2 inhibition leading to p35 cleavage and inhibition of subsequent p25/Cdk5 and caspase-8 overactivation.

scholarly journals Involvement of the miR-137-3p/CAPN-2 Interaction in Ischemia-Reperfusion-Induced Neuronal Apoptosis through Modulation of p35 Cleavage and Subsequent Caspase-8 Overactivation

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
He Wang ◽  
Qian Yu ◽  
Zai-Li Zhang ◽  
Hong Ma ◽  
Xiao-Qian Li
Keyword(s):  
Protein Expression ◽  
Motor Function ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Intrathecal Injection ◽  
Motor Dysfunction ◽  
Luciferase Assay ◽  
Caspase 8 ◽  
Neuron Survival

Background. Neuron survival after ischemia-reperfusion (IR) injury is the primary determinant of motor function prognosis. MicroRNA- (miR-) based gene therapy has gained attention recently. Our previous work explored the mechanisms by which miR-137-3p modulates neuronal apoptosis in both in vivo and in vitro IR models. Methods. IR-induced motor dysfunction and spinal calpain (CAPN) subtype expression and subcellular localization were detected within 12 h post IR. Dysregulated miRs, including miR-137-3p, were identified by miR microarray analysis and confirmed by PCR. A luciferase assay confirmed CAPN-2 as a corresponding target of miR-137-3p, and their modulation of motor function was evaluated by intrathecal injection with synthetic miRs. CAPN-2 activity was measured by the intracellular Ca2+ concentration and mean fluorescence intensity in vitro. Neuronal apoptosis was detected by flow cytometry and TUNEL assay. The activities of p35, p25, Cdk5, and caspase-8 were evaluated by ELISA and Western blot after transfection with specific inhibitors and miRs. Results. The IR-induced motor dysfunction time course was closely associated with upregulated expression of the CAPN-2 protein, which was mainly localized in neurons. The miR-137-3p/CAPN-2 interaction was confirmed by luciferase assay. The miR-137-3p mimic significantly improved IR-induced motor dysfunction and decreased CAPN-2 expression, even in combination with recombinant rat calpain-2 (rr-CALP2) injection, whereas the miR-137-3p inhibitor reversed these effects. Similar changes in the intracellular Ca2+ concentration, CAPN-2 expression, and CAPN-2 activity were observed when cells were exposed to oxygen-glucose deprivation and reperfusion (OGD/R) and transfected with synthetic miRs in vitro. Moreover, double fluorescence revealed identical neuronal localization of CAPN-2, p35, p25, and caspase-8. The decrease in CAPN-2 expression and activity was accompanied by the opposite changes in p35 activity and protein expression in cells transfected with the miR-137-3p mimic, roscovitine (a Cdk5 inhibitor), or Z-IETD-FMK (a caspase-8 inhibitor). Correspondingly, the abovementioned treatments resulted in a higher neuron survival rate than that of untreated neurons, as indicated by decreases in the apoptotic cell percentage and p25, Cdk5, caspase-8, and caspase-3 protein expression. Conclusions. The miR-137-3p/CAPN-2 interaction modulates neuronal apoptosis during IR injury, possibly by inhibiting CAPN-2, which leads to p35 cleavage and inhibition of subsequent p25/Cdk5 and caspase-8 overactivation.

scholarly journals Calycosin-7-O-β-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Xiangli Yan ◽  
Aiming Yu ◽  
Haozhen Zheng ◽  
Shengxin Wang ◽  
Yingying He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Pathological Process ◽  
Neuroprotective Effects ◽  
Ht22 Cells ◽  
Positive Effects ◽  
Antioxidant Stress

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

Triggering Receptor Expressed on Myeloid Cells 2, a Novel Regulator of Immunocyte Phenotypes, Confers Neuroprotection by Relieving Neuroinflammation

2017 ◽  
Vol 127 (1) ◽  
pp. 98-110 ◽  
Author(s):  
Qian Zhai ◽  
Feng Li ◽  
Xiyao Chen ◽  
Ji Jia ◽  
Sisi Sun ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Intraperitoneal Administration ◽  
Myeloid Cells ◽  
Glucose Deprivation ◽  
Interleukin 4 ◽  
Oxygen Glucose Deprivation

Abstract Background Microglia can not only detrimentally augment secondary injury but also potentially promote recovery. However, the mechanism underlying the regulation of microglial phenotypes after stroke remains unclear. Methods Mice were subjected to middle cerebral artery occlusion for 60 min. At 3 days after reperfusion, the effects of activation and suppression of triggering receptor expressed on myeloid cells 2 on immunocyte phenotypes (n = 5), neurobehavioral scores (n = 7), infarct volumes (n = 8), and neuronal apoptosis (n = 7) were analyzed. In vitro, cultured microglia were exposed to oxygen–glucose deprivation for 4 h. Inflammatory cytokines, cellular viability (n = 8), neuronal apoptosis (n = 7), and triggering receptor expressed on myeloid cells 2 expression (n = 5) were evaluated in the presence or absence of triggering receptor expressed on myeloid cell-specific small interfering RNA or triggering receptor expressed on myeloid cells 2 overexpression lentivirus. Results Triggering receptor expressed on myeloid cells 2 expression in the ischemic penumbra peaked at 3 days after ischemia–reperfusion injury (4.4 ± 0.1-fold, P = 0.0004) and was enhanced in interleukin-4/interleukin-13–treated microglia in vitro (1.7 ± 0.2-fold, P = 0.0119). After oxygen–glucose deprivation, triggering receptor expressed on myeloid cells 2 conferred neuroprotection by regulating the phenotypic conversion of microglia and inflammatory cytokine release. Intraperitoneal administration of triggering receptor expressed on myeloid cells 2 agonist heat shock protein 60 or unilateral delivery of a recombinant triggering receptor expressed on myeloid cells 2 lentivirus into the cerebral ventricle induced a significant neuroprotective effect in mice (apoptotic neurons decreased to 31.3 ± 7.6%; infarct volume decreased to 44.9 ± 5.3%). All values are presented as the mean ± SD. Conclusions Activation or up-regulation of triggering receptor expressed on myeloid cells 2 promoted the phenotypic conversion of microglia and decreased the number of apoptotic neurons. Our study suggests that triggering receptor expressed on myeloid cells 2 is a novel regulator of microglial phenotypes and may be a potential therapeutic target for stroke.

scholarly journals miR-19a/b-3p promotes inflammation during cerebral ischemia/reperfusion injury via SIRT1/FoxO3/SPHK1 pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Feng Zhou ◽  
Yu-Kai Wang ◽  
Cheng-Guo Zhang ◽  
Bing-Yi Wu
Keyword(s):  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Luciferase Assay ◽  
In Vivo Model ◽  
Tunel Staining

Abstract Background Stroke affects 3–4% of adults and kills numerous people each year. Recovering blood flow with minimal reperfusion-induced injury is crucial. However, the mechanisms underlying reperfusion-induced injury, particularly inflammation, are not well understood. Here, we investigated the function of miR-19a/b-3p/SIRT1/FoxO3/SPHK1 axis in ischemia/reperfusion (I/R). Methods MCAO (middle cerebral artery occlusion) reperfusion rat model was used as the in vivo model of I/R. Cultured neuronal cells subjected to OGD/R (oxygen glucose deprivation/reperfusion) were used as the in vitro model of I/R. MTT assay was used to assess cell viability and TUNEL staining was used to measure cell apoptosis. H&E staining was employed to examine cell morphology. qRT-PCR and western blot were performed to determine levels of miR-19a/b-3p, SIRT1, FoxO3, SPHK1, NF-κB p65, and cytokines like TNF-α, IL-6, and IL-1β. EMSA and ChIP were performed to validate the interaction of FoxO3 with SPHK1 promoter. Dual luciferase assay and RIP were used to verify the binding of miR-19a/b-3p with SIRT1 mRNA. Results miR-19a/b-3p, FoxO3, SPHK1, NF-κB p65, and cytokines were elevated while SIRT1 was reduced in brain tissues following MCAO/reperfusion or in cells upon OGD/R. Knockdown of SPHK1 or FoxO3 suppressed I/R-induced inflammation and cell death. Furthermore, knockdown of FoxO3 reversed the effects of SIRT1 knockdown. Inhibition of the miR-19a/b-3p suppressed inflammation and this suppression was blocked by SIRT1 knockdown. FoxO3 bound SPHK1 promoter and activated its transcription. miR-19a/b-3p directly targeted SIRT1 mRNA. Conclusion miR-19a/b-3p promotes inflammatory responses during I/R via targeting SIRT1/FoxO3/SPHK1 axis.

scholarly journals Saikokeishikankyoto extract alleviates muscle atrophy in KKAy mice

2022 ◽  
Author(s):  
Yanglan Ou ◽  
Kohei Jobu ◽  
Tomoaki Ishida ◽  
Shumpei Morisawa ◽  
Hiroko Fujita ◽  
...  
Keyword(s):  
Motor Function ◽  
Muscle Atrophy ◽  
Transcriptional Activity ◽  
Hot Water ◽  
Motor Dysfunction ◽  
Sirtuin 1 ◽  
Sarcopenic Obesity ◽  
Skeletal Muscle Atrophy ◽  
Kkay Mice

AbstractSarcopenic obesity is associated with increased visceral fat and decreased muscle mass, resulting in decreased insulin sensitivity, increased production of inflammatory cytokines, and oxidative stress. In this study, we first evaluated the effects of herbal medicines on the transcriptional activity of the Sirtuin 1 (sirt1) promoter in vitro as an indicator of their therapeutic effect. Our data suggested that hot water Saikokeishikankyoto (SKK) extracts increased sirt1 transcriptional activity in vitro, identifying it as a candidate therapeutic for evaluation in the KKAy type 2 diabetic obesity mouse model. These in vivo evaluations revealed that SKK treatment increased the wet weight and muscle fiber content in cross sections of the gastrocnemius muscle (GA) and restored motor function in these animals. In addition, SKK treatment reduced tumor necrosis factor-α (TNFα) expression in the sera and suppressed Atrogin1 and MuRF1 transcription in the GA samples. This treatment also increased sirt1 expression in these tissues. These results suggest that SKK inhibits skeletal muscle atrophy and improves motor function in KKAy mice by suppressing inflammation. In actual clinical practice, SKK is expected to inhibit muscle atrophy and improve motor dysfunction in sarcopenic obesity. Graphical abstract

scholarly journals LncRNA TUG1 regulates the development of ischemia-reperfusion mediated acute kidney injury through miR-494-3p/E-cadherin axis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Li Chen ◽  
Jun-Ying Xu ◽  
Hong-Bao Tan
Keyword(s):  
Acute Kidney Injury ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Luciferase Assay ◽  
Lncrna Tug1 ◽  
E Cadherin

AbstractBackgroundAcute kidney injury (AKI) results from renal dysfunction caused by various causes, resulting in high mortality. The underlying mechanisms of ischemia-reperfusion (I/R) induced AKI is very complicated and needed for further research. Here, we sought to found out the functions of lncRNA TUG1 in I/R-induced AKI.MethodsIn vivo model was constructed by I/R-induced mice and in vitro model was constructed by hypoxia/reoxygenation (H/R)-induced HK-2 cell. Kidney tissue damage was evaluated through H&E staining in mice. Cell flow cytometry was used to detect the degree of apoptosis. TUG1, miR-494-3p and E-cadherin were determined both by RT-PCR and western blot. Dual luciferase assay was employed to validate the relationships between TUG1, miR-494-3p and E-cadherin. Inflammatory factors including IL-1β, TNFɑ and IL-6 were evaluated by ELISA.ResultslncRNA TUG1 was decreased while miR-494-3p was elevated in vivo and in vitro. Overexpression of TUG1 or transfection with miR-494-3p inhibitor significantly alleviated cell apoptosis. MiR-494-3p directly targeted E-cadherin and TUG1 suppressed cell apoptosis via serving as a miR-494-3p sponge to disinhibit E-cadherin.ConclusionlncRNA TUG1 alleviated I/R-induced AKI through targeting miR-494-3p/E-cadherin.

scholarly journals QKI 6 ameliorates CIRI through promoting synthesis of triglyceride in neuron and inhibiting neuronal apoptosis associated with SIRT1-PPARγ-PGC-1α axis

2020 ◽  
Author(s):  
Rui Liu ◽  
Hongzeng Li ◽  
Jingyuan Deng ◽  
Qunqiang Wu ◽  
Chunhua Liao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Rna Binding ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Post Transcriptional Regulation

AbstractThe stroke induced by ischemia of brain remains high incidence and death rate. The study wanted to confirm the effects of QKI 6 on the protection role in neurons of rat model of cerebral ischemia/reperfusion injury (CIRI). The rat model with CIRI induced by MCAO (middle cerebral artery occlusion) was well established and rat neurons were isolated to characterize the effects of QKI 6 mediated by SIRT1 on synthesis of triglyceride in neuron and neuronal apoptosis via activation of SIRT1-PPARγ-PGC-1α signaling pathway. The expression levels of SIRT1 or QKI 6, and acetylation level of QKI 6 was decreased in neurons of rat model with CIRI. QKI 6 deacetylated and mediated by SIRT1 that contributed to suppressing the progression of neuronal apoptosis in rat through promoting synthesis of triglyceride in vivo and in vitro via SIRT1-PPARγ-PGC-1α signaling pathway, then inhibiting CIRI. In conclusion, our results demonstrated SIRT1 deacetylates QKI 6, the RNA-binding protein, that affects significantly the synthesis of triglyceride in neurons of CIRI rat model. Moreover, it activated transcription factor PGC-1α through post-transcriptional regulation of the expression of PPARγ, and further enhanced synthesis of triglyceride, thereby restrained the progression of neural apoptosis and CIRI.

A naturally occurring FXR agonist, alisol B 23-acetate, protects against renal ischemia-reperfusion injury

2021 ◽  
Author(s):  
Zhi-Lin Luan ◽  
Wen-Hua Ming ◽  
Xiao-Wan Sun ◽  
Cong Zhang ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Farnesoid X Receptor ◽  
Site Directed Mutagenesis ◽  
Luciferase Assay ◽  
Naturally Occurring

The ligand-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating renal function. Activation of FXR by its specific agonists exerts renoprotective action in animals with acute kidney injury (AKI). In the present study, we aimed to identify naturally occurring agonists of FXR with potential as therapeutic agents in renal ischemia-perfusion injury (IRI). In vitro and in vivo FXR activation was determined by dual-luciferase assay, docking analysis, site-directed mutagenesis, and whole kidney transcriptome analysis. Wild-type (WT) and FXR knockout (FXR-/-) mice were used to determine the effect of potential FXR agonist on renal IRI. We found that alisol B 23-acetate (ABA), a major active triterpenoid extracted from Alismatis Rhizoma, a well-known traditional Chinese medicine, can activate renal FXR and induce FXR downstream gene expression in mouse kidney. ABA treatment significantly attenuated renal IR-induced AKI in WT mice but not in FXR-/- mice. Our results demonstrate that ABA can activate renal FXR to exert renoprotection against IRI-induced AKI. Therefore, ABA may represent a potential therapeutic agent in the treatment of ischemic AKI.

Role of miR-323b-5p in Inflammation, Oxidative Stress and Apoptosis During Cerebral Ischemia/Reperfusion Injury

2019 ◽  
Vol 9 (6) ◽  
pp. 829-838
Author(s):  
Chuan Liu ◽  
Juan Du ◽  
Zhaohui Wang ◽  
Fanhua Meng
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Luciferase Assay ◽  
Ros Generation ◽  
Wild Type ◽  
Induced Expression ◽  
Cerebral Ischemia Reperfusion

Objective: The aims of this study is to investigate the potential effects of miR-323b-5p in an in vitro cerebral ischemia-reperfusion (I/R) model via targeting BCL2L11. Materials and methods: PC-12 cells exposed to oxygen-glucose deprivation/reperfusion condition (OGD/R) were classified into control, OGD/R model, miR-323b-5p inhibitor, inhibitor NC, sh-BCL2L11, shRNA NC, miR-323b5p inhibitor + shRNA NC, miR-323b-5p inhibitor + sh-BCL2L11, as well as the wild type cells. Cell apoptosis was observed by flow cytometry. The targeting relationship between miR-323b-5p and BCL2L11 was verified by luciferase assay. ELISA, qRT-PCR, and Western blot were performed to evaluate expressions of related molecules. Results: Compared with wild type, OGD/R significantly induced expression level of miR-323b-5p. In addition, downregulation of miR-323b-5p suppressed the OGD/R induced expression of pro-inflammation factors such as TNFα, IL-1β, IL-6 and monocyte chemotactic protein-1 (MCP-1), OGD/R induced reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) release. Increased ROS often leads to increased levels of malondialdehyde (MDA) and decreased anti-oxidants super oxide dismutase (SOD), and these OGD/R induced results were reversed by downregulation of miR-323b-5p. Decreased miR-323b-5p also inhibited the OGD/R induced apoptosis. Moreover, miR-323b-5p mediated apoptosis was mediated by directly targeting BCL2L11. Conclusions: miR-323b-5p may regulate cerebral I/R injury by targeting BCL2L11 and is a potential therapeutic and diagnostic biomarker for cerebral I/R injury.

scholarly journals MiR-298 Exacerbates Ischemia/Reperfusion Injury Following Ischemic Stroke by Targeting Act1

2018 ◽  
Vol 48 (2) ◽  
pp. 528-539 ◽  
Author(s):  
Hongxue Sun ◽  
Di Zhong ◽  
Cheng Wang ◽  
Yilei Sun ◽  
Jiaying Zhao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Luciferase Assay ◽  
Regulatory Relationship

Background/Aims: This study investigated the role of the microRNA miR-298 and its target Act1 in ischemic stroke. Methods: Cell viability was assessed with the 3-(4,5-dimethythiazol-2- yl)-2,5-diphenyl tetrazolium bromide assay. Apoptotic cells were detected by flow cytometry, and mRNA and protein expression were assessed by quantitative real-time PCR and western blotting, respectively. The regulatory relationship between miR-298 and Act1 was evaluated with the luciferase assay. To clarify the role of Act1 following ischemic stroke, the transcript was knocked down by short interfering RNA. The in vitro findings were validated in a mouse model of middle cerebral artery occlusion by administration of miR-298 mimic. Results: Act1 was upregulated whereas miR-298 was downregulated in ischemic stroke. miR-298 overexpression by transfection of a mimic suppressed Act1 protein levels in vitro and in vivo, and the luciferase assay showed that miR-298 directly binds to the 3’ untranslated region of the Act1 transcript. miR-298 overexpression enhanced cell apoptosis and autophagy and exacerbated ischemic infarction and neurological deficits, effects that were exerted via negative regulation of Act1/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB signaling and downstream autophagy pathways. Conclusions: Upregulation of miR-298 following ischemic stroke promotes brain injury in vitro and vivo by inhibiting the Act1/JNK/NF-κB signaling cascade and the downstream autophagy pathway. Therapeutic strategies that target miR-298 could be beneficial for the treatment of ischemic stroke.

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