The Molecular Functions of MeCP2 in Rett Syndrome Pathology

Osman, Sharifi; Yasui, Dag H.

doi:10.3389/fgene.2021.624290

Cited by 24 publications

(20 citation statements)

References 142 publications

(214 reference statements)

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“…24 It has been reported that MECP2 plays a pivotal role in Rett syndrome pathology and a novel double mutation that can affect the transcription repression domain of MECP2 and cause a severe phenotype of Rett syndrome. [25][26][27] The results of our study reported here show that MECP2, the target of miR-205 in tenocytes was identified as an important transcriptional inhibitor, which might be a novel critical factor in the proliferation, migration and fibrosis of tenocytes.…”

Section: Discussionmentioning

confidence: 60%

Inhibition of miR-205 promotes proliferation, migration and fibrosis of tenocytes through targeting MECP2: Implications for rotator cuff injury

Mao¹,

Yin²

2022

Adv Clin Exp Med

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Background. The production of inflammatory mediators is critical for tenocytes proliferation and migration, which play an important role in rotator cuff injury repair and regulation of collagen. MicroRNA (miRNA)-205 (miR-205) promotes the secretion of inflammatory factors. The mechanism of the tenocytes regulation by miR-205 remains unknown. In this paper, we showed that miR-205 can regulate the proliferation, migration and fibrosis of tenocytes.Objectives. To investigate the function and mechanism of miR-205/MeCP2 pathway on the proliferation, migration and fibrosis of rotator cuff tenocytes, in order to provide a new perspective on the repair of rotator cuff tear injury. Materials and methods.The tenocytes were collected under sterile conditions from the Achilles tendons of Sprague Dawley (SD) rats (weighing 150-200 g). The cells of passages 2-4 were used for the following experiments. All miRNA and vectors were transfected with Lipofectamine 2000. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR), Cell Counting Kit-8 (CCK-8) assay, luciferase reporter assay, and migration assay were performed. Then, immunoblotting analysis and statistical analysis were conducted.Results. The CCK-8 and migration assay revealed that miR-205 inhibition resulted in increased tenocytes proliferation, migration and fibrosis. The miR-205 reduced the mRNA and protein expression levels of MECP2, which is involved in cell proliferation and migration of tenocytes. The miR-205 inhibited luciferase intensity under the control of the 3'UTRs of MECP2.Conclusions. The inhibition of MECP2 reversed the effect of miR-205 inhibitor on tenocytes, including the proliferation and migration of tenocytes, indicating that miR-205 may be valuable in miRNA-based therapies for rotator cuff injury.

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Section: Discussionmentioning

confidence: 60%

Inhibition of miR-205 promotes proliferation, migration and fibrosis of tenocytes through targeting MECP2: Implications for rotator cuff injury

Mao¹,

Yin²

2022

Adv Clin Exp Med

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“…3). The dependence of these phases of response of W to PSI on the dual regulation of bdnf by MeCP2 suggests that the special MeCP2 binding kinetics may provide a possible explanation of complex effects of MeCP2 on gene expression [28-29, 48] and a potential therapeutic target for rescuing memory impaired by disruptions.…”

Section: Discussionmentioning

confidence: 99%

“…1). The effects of MeCP2 on gene expression are complex [28–29]. MeCP2 can act as a repressor or activator of BDNF transcription depending on context.…”

Section: Methods: Model Developmentmentioning

confidence: 99%

Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: critical roles of CaMKIIα and MeCP2

Zhang

Smolen

Alberini

et al. 2022

Preprint

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Key features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) dependent feedback loops. We investigated the ways in which these pathways may contribute to developmental and dynamical features of consolidation. A computational model of molecular processes underlying consolidation following inhibitory avoidance (IA) training in rats was developed. Differential equations described the actions of CaMKIIα, multiple feedback loops regulating BDNF expression, and several transcription factors including methyl-CpG binding protein 2 (MeCP2), histone deacetylase 2 (HDAC2), and SIN3 transcription regulator family member A (Sin3a). This model provides novel explanations for the (apparent) rapid forgetting of infantile memory and the temporal progression of memory consolidation in adults. Simulations predict that dual effects of MeCP2 on the expression of bdnf, and interaction between MeCP2 and CaMKIIα, play critical roles in the rapid forgetting of infantile memory and the progress of memory resistance to disruptions. These insights suggest new potential targets of therapy for memory impairment.

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“…Thus, we included a BDNF-CaMKIIα-BDNF positive feedback loop (Fig 1A . The effects of MeCP2 on gene expression are complex [28,29]. MeCP2 can act as a repressor or activator of BDNF transcription depending on context.…”

Section: Introductionmentioning

confidence: 99%

Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: Critical roles of CaMKIIα and MeCP2

et al. 2022

View full text Add to dashboard Cite

Key features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα) dependent feedback loops. We investigated the ways in which these pathways may contribute to developmental and dynamical features of consolidation. A computational model of molecular processes underlying consolidation following inhibitory avoidance (IA) training in rats was developed. Differential equations described the actions of CaMKIIα, multiple feedback loops regulating BDNF expression, and several transcription factors including methyl-CpG binding protein 2 (MeCP2), histone deacetylase 2 (HDAC2), and SIN3 transcription regulator family member A (Sin3a). This model provides novel explanations for the (apparent) rapid forgetting of infantile memory and the temporal progression of memory consolidation in adults. Simulations predict that dual effects of MeCP2 on the expression of bdnf, and interaction between MeCP2 and CaMKIIα, play critical roles in the rapid forgetting of infantile memory and the progress of memory resistance to disruptions. These insights suggest new potential targets of therapy for memory impairment.

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The Molecular Functions of MeCP2 in Rett Syndrome Pathology

Cited by 24 publications

References 142 publications

Inhibition of miR-205 promotes proliferation, migration and fibrosis of tenocytes through targeting MECP2: Implications for rotator cuff injury

Inhibition of miR-205 promotes proliferation, migration and fibrosis of tenocytes through targeting MECP2: Implications for rotator cuff injury

Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: critical roles of CaMKIIα and MeCP2

Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: Critical roles of CaMKIIα and MeCP2

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