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Bincheng Wang - One of the best experts on this subject based on the ideXlab platform.

  • sirt1 exerts neuroprotective effects by attenuating cerebral ischemia reperfusion induced injury via targeting p53 microRNA 22
    International Journal of Molecular Medicine, 2017
    Co-Authors: Bincheng Wang
    Abstract:

    The aim of this study was to investigate whether the SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury (CIRI) via targeting p53/microRNA-22. We found that the overexpression of sirtuin 1 (SIRT1) decreased the infarct volume, suppressed p53 protein expression and activated microRNA-22 expression following CIRI. An injection of lipopolysaccharide (LPS, 1 mg/ml; Sigma, St. Louis, MO USA) into the corpus callosum was used to induce CIRI in rats. The infarct volume and neurological deficit score were used to examine the effects of SIRT1 on CIRI. Furthermore, the overexpression of SIRT1 was found to suppress caspase-3 activity, inhibit the activation of the Bax signaling pathway, reduce tumor necrosis factor-α (TNF-α) and interleukin (IL)-6) activity, decrease cyclooxygenase (COX)‑2 and inducible nitric oxide synthase (iNOS) protein expression, and increase IL-10 activity following CIRI. Following the downregulation of SIRT1, p53 protein expression was significantly increased, microRNA-22 expression was inhibited, caspase-3 activity was increased and the Bax signaling pathway was activated. In addition, the activity of TNF-α and IL-6 was was enhanced, COX-2 and iNOS protein expression was increased, and IL-10 activity was reduced following CIRI. Thus, the data from our study suggest that SIRT1 attenuates CIRI by targeting the p53/microRNA-22 axix, while suppressing apoptosis, inflammation, COX-2 and iNOS expression.

  • SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury via targeting p53/microRNA-22.
    International journal of molecular medicine, 2016
    Co-Authors: Bincheng Wang
    Abstract:

    The aim of this study was to investigate whether the SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury (CIRI) via targeting p53/microRNA-22. We found that the overexpression of sirtuin 1 (SIRT1) decreased the infarct volume, suppressed p53 protein expression and activated microRNA-22 expression following CIRI. An injection of lipopolysaccharide (LPS, 1 mg/ml; Sigma, St. Louis, MO USA) into the corpus callosum was used to induce CIRI in rats. The infarct volume and neurological deficit score were used to examine the effects of SIRT1 on CIRI. Furthermore, the overexpression of SIRT1 was found to suppress caspase-3 activity, inhibit the activation of the Bax signaling pathway, reduce tumor necrosis factor-α (TNF-α) and interleukin (IL)-6) activity, decrease cyclooxygenase (COX)‑2 and inducible nitric oxide synthase (iNOS) protein expression, and increase IL-10 activity following CIRI. Following the downregulation of SIRT1, p53 protein expression was significantly increased, microRNA-22 expression was inhibited, caspase-3 activity was increased and the Bax signaling pathway was activated. In addition, the activity of TNF-α and IL-6 was was enhanced, COX-2 and iNOS protein expression was increased, and IL-10 activity was reduced following CIRI. Thus, the data from our study suggest that SIRT1 attenuates CIRI by targeting the p53/microRNA-22 axix, while suppressing apoptosis, inflammation, COX-2 and iNOS expression.

Hanqing Zhao - One of the best experts on this subject based on the ideXlab platform.

  • microRNA-22 regulates smooth muscle cell differentiation from stem cells by targeting methyl CpG-binding protein 2.
    Arteriosclerosis thrombosis and vascular biology, 2015
    Co-Authors: Hanqing Zhao, Guanmei Wen, Yuan Huang, Qishan Chen, Tayyab Adeel Afzal, Le Anh Luong, Jianhua Zhu, Li Zhang
    Abstract:

    Objective—In this study, we attempted to uncover the functional impact of microRNA-22 (miR-22) and its target gene in smooth muscle cell (SMC) differentiation and delineate the molecular mechanism ...

  • Abstract 004: microRNA-22 Regulates Smooth Muscle Cell Differentiation From Stem Cells By Targeting Methyl Cpg Binding Protein 2
    Circulation Research, 2013
    Co-Authors: Hanqing Zhao, Guanmei Wen, Yuan Huang, Wen Wang, Qingzhong Xiao
    Abstract:

    Objectives: To investigate the role of microRNA-22 (miR-22) in smooth muscle cell (SMC) differentiation from stem cells and the molecular mechanism involved. Methods and Results: Mouse embryonic stem (ES) cells were seeded on collagen IV-coated flasks and cultured in the absence of Leukemia Inhibitory Factor in differentiation medium for 4 to 8 days in order to induce SMCs differentiation. We found that miR-22 was significantly up-regulated during SMC differentiation. Enforced expression of miR-22 by its mimic in differentiating ES cells significantly up-regulated expression of a panel of SMC-specific genes, while knock-down of miR-22 by its antagomiR decreased these gene expression at both RNA and protein levels. Furthermore, we found over-expression and knockdown of miR-22 up-regulated and down-regulated SMC transcription factor SRF and its co-activator myocardin in a similar manner, respectively, and miR-22 overexpression in stem cells promoted SMC differentiation in vivo . Transcription repressor methyl CpG binding protein 2 (MECP2) was predicted as one of the top targets of miR-22 by using several computational miRNA target prediction tools. Interestingly, the gene expression levels of MECP2 were significantly decreased during SMC differentiation in a time dependent manner. Moreover, MECP2 was dramatically decreased in miR-22 overexpressing cells, but significantly increased when miR-22 was knockdown in the differentiating stem cells. Importantly, luciferase assay showed miR-22 substantially inhibited wild type MECP2-3’-UTR-luciferase activity in differentiating ES cells, but not mutant MECP2-3’-UTR-luciferease reporter. In addition, modulation of MECP2 expression levels affect multiple SMC-specific marker gene expression in differentiated ES cells by conducting gain-of-function experiments using MECP2 expression plasmid. Finally, we tested the expression of miR-22 in mouse femoral artery denudation injury model and found that miR-22 was significantly down-regulated in the wire injury-induced neointimal formation as early as day 3 post-injury. Conculsion: Using genomic and functional studies, we have discovered miR-22 controls SMC differentiation from stem cells via modulating MECP2 expression and function.

Jialiang Mao - One of the best experts on this subject based on the ideXlab platform.

  • Simvastatin inhibits inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages through the microRNA-22/Cyr61 axis.
    International journal of clinical and experimental pathology, 2018
    Co-Authors: Bingxu Chen, Shengheng Zhou, Jialiang Mao
    Abstract:

    Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to improve atherosclerosis (AS) via its anti-inflammatory activity. Recently, several studies have reported the involvement of macrophages in chronic inflammation associated with AS. However, it is unknown whether macrophages participate in the anti-inflammatory activity of simvastatin in AS. This study was designed to investigate the roles and underlying mechanisms of simvastatin in LPS-stimulated RAW264.7 macrophages. First, we examined the anti-inflammatory effects of simvastatin on LPS-treated macrophage RAW264.7 cells using an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Then, a microarray assay was used to analyze the microRNA (miRNA) expression profile in RAW264.7 cells incubated with or without simvastatin in the presence of LPS. microRNA-22 (miR-22) with the highest change was validated independently by qRT-PCR. Luciferase reporter assays were conducted to determine the association between miR-22 and the cysteine-rich protein 61 (Cyr61). Subsequently, we investigated the molecular mechanism by which miR-22 functions in the anti-inflammation of simvastatin in LPS-stimulated macrophages. We found that simvastatin treatment could significantly inhibit inflammation by modulating the expression of mediators, such as IL-1β, TNF-α and IL-6, whose expression were increased remarkably in the activated RAW264.7 cells. miR-22 was found to be one of the most significantly upregulated miRNAs in LPS-stimulated RAW264.7 macrophages after treatment with simvastatin. Pre-treatment of simvastatin in LPS-stimulated RAW264.7 macrophages enhanced miR-22 expression in a dose dependent manner. Interestingly, Cyr61, a novel pro-inflammatory factor involved in the pathogenesis of atherosclerosis (AS), was identified as a direct target of miR-22. Overexpression of miR-22 enhanced the anti-inflammatory effects of simvastatin, whereas inhibition of miR-22 had an opposite effect. More importantly, further study demonstrated that the knockdown of Cyr61 by siRNA could attenuate the inhibitory effects of miR-22 inhibition on anti-inflammatory activities of simvastatin. The results clearly show that simvastatin inhibits the inflammation response in LPS-stimulated RAW264.7 macrophages through the miR-22/Cyr61 axis and suggests that targeting the miR-22/Cyr61 axis may be a promising molecular target for AS therapy.

  • simvastatin inhibits inflammatory response in lipopolysaccharide lps stimulated raw264 7 macrophages through the microRNA 22 cyr61 axis
    International Journal of Clinical and Experimental Pathology, 2018
    Co-Authors: Bingxu Chen, Shengheng Zhou, Jialiang Mao
    Abstract:

    Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to improve atherosclerosis (AS) via its anti-inflammatory activity. Recently, several studies have reported the involvement of macrophages in chronic inflammation associated with AS. However, it is unknown whether macrophages participate in the anti-inflammatory activity of simvastatin in AS. This study was designed to investigate the roles and underlying mechanisms of simvastatin in LPS-stimulated RAW264.7 macrophages. First, we examined the anti-inflammatory effects of simvastatin on LPS-treated macrophage RAW264.7 cells using an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Then, a microarray assay was used to analyze the microRNA (miRNA) expression profile in RAW264.7 cells incubated with or without simvastatin in the presence of LPS. microRNA-22 (miR-22) with the highest change was validated independently by qRT-PCR. Luciferase reporter assays were conducted to determine the association between miR-22 and the cysteine-rich protein 61 (Cyr61). Subsequently, we investigated the molecular mechanism by which miR-22 functions in the anti-inflammation of simvastatin in LPS-stimulated macrophages. We found that simvastatin treatment could significantly inhibit inflammation by modulating the expression of mediators, such as IL-1β, TNF-α and IL-6, whose expression were increased remarkably in the activated RAW264.7 cells. miR-22 was found to be one of the most significantly upregulated miRNAs in LPS-stimulated RAW264.7 macrophages after treatment with simvastatin. Pre-treatment of simvastatin in LPS-stimulated RAW264.7 macrophages enhanced miR-22 expression in a dose dependent manner. Interestingly, Cyr61, a novel pro-inflammatory factor involved in the pathogenesis of atherosclerosis (AS), was identified as a direct target of miR-22. Overexpression of miR-22 enhanced the anti-inflammatory effects of simvastatin, whereas inhibition of miR-22 had an opposite effect. More importantly, further study demonstrated that the knockdown of Cyr61 by siRNA could attenuate the inhibitory effects of miR-22 inhibition on anti-inflammatory activities of simvastatin. The results clearly show that simvastatin inhibits the inflammation response in LPS-stimulated RAW264.7 macrophages through the miR-22/Cyr61 axis and suggests that targeting the miR-22/Cyr61 axis may be a promising molecular target for AS therapy.

Xiao Chuan Sun - One of the best experts on this subject based on the ideXlab platform.

  • neuroprotective effects of p53 microRNA 22 regulate inflammation and apoptosis in subarachnoid hemorrhage
    International Journal of Molecular Medicine, 2018
    Co-Authors: Yi Jun Zeng, Xiao Chuan Sun
    Abstract:

    The present study aimed to investigate whether the neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage (SAH). In a mouse model of SAH, microRNA‑22 expression was upregulated. In addition, downregulation of microRNA‑22 in HEB cells increased the mRNA expression levels of interleukin (IL)‑6, induced cysteine rich angiogenic inducer 61 (Cyr61) expression, and suppressed the protein expression levels of B‑cell lymphoma 2‑associated X protein (Bax) and caspase‑3 activity. Treatment with the p53 inhibitor, pifithrin‑α, suppressed p53 protein expression, increased IL‑6 mRNA expression, decreased microRNA‑22 expression, Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in mice with SAH. Furthermore, p53 expression was knocked down using p53 small interfering RNA, which suppressed microRNA‑22 expression and increased IL‑6 mRNA expression, inhibited Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in HEB cells. The present study demonstrated that the neuroprotective effects of p53/microRNA‑22 may regulate inflammation and apoptosis in SAH. Reverse transcription quantitative polymerase chain reaction (qPCR) was used to analyze the expression of microRNA-22, western blot analysis was used to analyze the protein expression of Bax and Cyr61.

  • Neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage.
    International journal of molecular medicine, 2018
    Co-Authors: Yi Jun Zeng, Xiao Chuan Sun
    Abstract:

    The present study aimed to investigate whether the neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage (SAH). In a mouse model of SAH, microRNA‑22 expression was upregulated. In addition, downregulation of microRNA‑22 in HEB cells increased the mRNA expression levels of interleukin (IL)‑6, induced cysteine rich angiogenic inducer 61 (Cyr61) expression, and suppressed the protein expression levels of B‑cell lymphoma 2‑associated X protein (Bax) and caspase‑3 activity. Treatment with the p53 inhibitor, pifithrin‑α, suppressed p53 protein expression, increased IL‑6 mRNA expression, decreased microRNA‑22 expression, Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in mice with SAH. Furthermore, p53 expression was knocked down using p53 small interfering RNA, which suppressed microRNA‑22 expression and increased IL‑6 mRNA expression, inhibited Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in HEB cells. The present study demonstrated that the neuroprotective effects of p53/microRNA‑22 may regulate inflammation and apoptosis in SAH. Reverse transcription quantitative polymerase chain reaction (qPCR) was used to analyze the expression of microRNA-22, western blot analysis was used to analyze the protein expression of Bax and Cyr61.

Qingzhong Xiao - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 004: microRNA-22 Regulates Smooth Muscle Cell Differentiation From Stem Cells By Targeting Methyl Cpg Binding Protein 2
    Circulation Research, 2013
    Co-Authors: Hanqing Zhao, Guanmei Wen, Yuan Huang, Wen Wang, Qingzhong Xiao
    Abstract:

    Objectives: To investigate the role of microRNA-22 (miR-22) in smooth muscle cell (SMC) differentiation from stem cells and the molecular mechanism involved. Methods and Results: Mouse embryonic stem (ES) cells were seeded on collagen IV-coated flasks and cultured in the absence of Leukemia Inhibitory Factor in differentiation medium for 4 to 8 days in order to induce SMCs differentiation. We found that miR-22 was significantly up-regulated during SMC differentiation. Enforced expression of miR-22 by its mimic in differentiating ES cells significantly up-regulated expression of a panel of SMC-specific genes, while knock-down of miR-22 by its antagomiR decreased these gene expression at both RNA and protein levels. Furthermore, we found over-expression and knockdown of miR-22 up-regulated and down-regulated SMC transcription factor SRF and its co-activator myocardin in a similar manner, respectively, and miR-22 overexpression in stem cells promoted SMC differentiation in vivo . Transcription repressor methyl CpG binding protein 2 (MECP2) was predicted as one of the top targets of miR-22 by using several computational miRNA target prediction tools. Interestingly, the gene expression levels of MECP2 were significantly decreased during SMC differentiation in a time dependent manner. Moreover, MECP2 was dramatically decreased in miR-22 overexpressing cells, but significantly increased when miR-22 was knockdown in the differentiating stem cells. Importantly, luciferase assay showed miR-22 substantially inhibited wild type MECP2-3’-UTR-luciferase activity in differentiating ES cells, but not mutant MECP2-3’-UTR-luciferease reporter. In addition, modulation of MECP2 expression levels affect multiple SMC-specific marker gene expression in differentiated ES cells by conducting gain-of-function experiments using MECP2 expression plasmid. Finally, we tested the expression of miR-22 in mouse femoral artery denudation injury model and found that miR-22 was significantly down-regulated in the wire injury-induced neointimal formation as early as day 3 post-injury. Conculsion: Using genomic and functional studies, we have discovered miR-22 controls SMC differentiation from stem cells via modulating MECP2 expression and function.