Peroxisome Proliferator-Activated Receptor δ Regulation of miR-15a in Ischemia-Induced Cerebral Vascular Endothelial Injury

Yin, Ke‐Jie; Deng, Zhen; Hamblin, Milton; Xiang, Ye; Huang, Huarong; Zhang, Jifeng; Jiang, Xiao-dan; Wang, Yanzhuang; Chen, Y. Eugene

doi:10.1523/jneurosci.0780-10.2010

Cited by 186 publications

(172 citation statements)

References 59 publications

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“…For example, miR-15a expression is increased in vascular endothelial cells following acute OGD, and was demonstrated to inhibit expression of Conversely, SIRT1 can increase gene expression through deacetylating lysine residues within a lysine-glycine repeat region in DNMT1 thereby reducing DNMT1 activity leading to DNA hypomethylation, and through the deacetylation-dependent activation of transcription factors (TF) and inactivation of transcriptional repressors such as methyl-CpG binding protein 2 (MeCP2) the anti-apoptotic gene B-cell lymphoma 2 (bcl-2) leading to cell death. Inhibition of miRNA-15a expression in vivo increased bcl-2 protein levels, and reduced cerebral infarct volume in mice following 60 min of MCAO [59]. Similarly, miR-497 expression was increased following transient MCAO and was demonstrated to inhibit bcl-2 and bcl-w expression.…”

Section: Sumoylationmentioning

confidence: 88%

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

et al. 2013

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Ischemic preconditioning is an innate neuroprotective mechanism in which a sub-injurious ischemic exposure increases the brain's ability to withstand a subsequent, normally injurious ischemic insult. Part of ischemic preconditioning neuroprotection stems from an epigenetic reprogramming of the brain to a phenotype of ischemic tolerance, which results in a gene expression profile different from that observed in the non-injured and ischemia-injured brains. Such neuroprotective reprograming, activated by ischemic preconditioning, requires specific changes in DNA accessibility coordinated with activation of transcriptional activator and repressor proteins, which allows for expression of specific neuroprotective proteins despite a general repression of gene expression. In this review we examine the effects of injurious ischemia and ischemic preconditioning on the regulation of DNA methylation, histone post-translational modifications, and non-coding RNA expression. There is increasing interest in the role of epigenetics in disease pathobiology, and whether and how pharmacological manipulation of epigenetic processes may allow for ischemic neuroprotection. Therefore, a better understanding of the epigenomic determinants underlying the modulation of gene expression that lead to ischemic tolerance or cell death offers the promise of novel neuroprotective therapies that target global reprograming of genomic activity versus individual cellular signaling pathways.

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Section: Sumoylationmentioning

confidence: 88%

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

et al. 2013

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“…The miR-15a/ 16-1 cluster is the first group of identified miR genes associated with mammalian carcinogenesis (16,17). In our previous publication (18), we demonstrated that miR-15a, by negatively regulating the Bcl-2 protein, has an anti-survival role in oxygenglucose deprivation-induced cerebral vascular endothelial cell death. Additionally, recent studies have shown that miR-16-1 displays anti-angiogenic characteristics by directly inhibiting VEGF protein expression in carcinoma cell lines (19 -21) as well as in endothelial cells (22).…”

mentioning

confidence: 82%

“…The brains were removed, homogenized, and purified to isolate cerebral microvessels by a previously described method (18).…”

Section: Generation Of Ec-selective Mir-15a Transgenic (Ec-mir-15a Tg)mentioning

confidence: 99%

“…The relative microRNA levels were measured by the TaqMan MiRNA Reverse Transcription kit and MiRNA Assay kit (18,30).…”

Section: Generation Of Ec-selective Mir-15a Transgenic (Ec-mir-15a Tg)mentioning

confidence: 99%

“…The cells were also co-transfected with a FGF2 or VEGFa 3Ј-UTR luciferase reporter vector and a Renilla luciferase control reporter vector (pRL-TK), along with Lipofectamine 2000 (Invitrogen) for 4 h. Luciferase activity was determined 48 h after transfection using Dual-Luciferase assay kits (Promega) and a luminometer (Turner Designs). Individual luciferase activity was normalized to the corresponding Renilla-luciferase activity (18,30).…”

Section: Generation Of Lentivirus To Achieve Gain-or Loss-of-mir-15a mentioning

confidence: 99%

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Vascular Endothelial Cell-specific MicroRNA-15a Inhibits Angiogenesis in Hindlimb Ischemia

Yin

Olsen

Hamblin

et al. 2012

Journal of Biological Chemistry

123

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Background: MicroRNAs mediate angiogenesis in both physiological and pathological conditions, but underlying molecular mechanisms are largely unexplored. Results: Endothelial miR-15a negatively regulates angiogenesis in vivo and in vitro by suppression of FGF2 and VEGF. Conclusion: MiR-15a inhibits endothelial autonomous angiogenesis. Significance: MiR-15a is a negative regulator of angiogenesis and a potential target for the restorative therapy of ischemic diseases.

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Therapeutic anti‐amyloid β antibodies cause neuronal disturbances

Adhikari

Khan

Mikhael

et al. 2022

Alzheimer's & Dementia

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Recent published clinical trial safety data showed that 41% of Alzheimer patients experienced amyloid-related imaging abnormalities (ARIA), marks of microhemorrhages and oedema in the brain, following administration of Biogen's Aduhelm/ aducanumab (amino acids 3-7 of the Aβ peptide). Similarly, Janssen/Pfizer's Bapineuzumab (amino acids 1-5 of the Aβ peptide) and Roche's Gantenerumab (amino acids 2-11/18-27 of the Aβ peptide) also displayed ARIA in clinical trials, including microhemorrhage and focal areas of inflammation or vasogenic oedema respectively. The molecular mechanisms underlying ARIA caused by therapeutic anti-Aβ antibodies remain largely unknown, however, recent reports demonstrated that therapeutic antiprion antibodies activate both neuronal apoptotic and allergenic proteomes following cross-linking cellular prion protein. Here, we report that treatment of human induced pluripotent stem cellsderived neurons (HSCN) from a non-demented donor, co-cultured with human primary microglia with anti-Aβ1-6, or anti-Aβ17-23 antibodies activate a significant number of both apoptotic and allergenic-related proteins as assessed by mass spectrometry. Interestingly, a large proportion of the identified proteins included cytokines such as IL-4, IL-12, and IL-13 suggesting a type-1 hypersensitivity response. Following flow cytometry analysis, several proinflammatory cytokines were significantly elevated following anti-Aβ1-6, or anti-Aβ17-23 antibody treatment. These results justify further and more robust investigation of the molecular mechanisms of ARIA during immunotherapy study trials of AD.

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Peroxisome Proliferator-Activated Receptor δ Regulation of miR-15a in Ischemia-Induced Cerebral Vascular Endothelial Injury

Cited by 186 publications

References 59 publications

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

Vascular Endothelial Cell-specific MicroRNA-15a Inhibits Angiogenesis in Hindlimb Ischemia

Therapeutic anti‐amyloid β antibodies cause neuronal disturbances

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