<scp>RNA</scp>i‐mediated ephrin‐B2 silencing attenuates astroglial‐fibrotic scar formation and improves spinal cord axon growth

Li, Yi; Chen, Ying; Tan, Ling; Pan, Jingying; Wei, Lin; Wu, Jian; Hu, Wen; Chen, Xue; Wang, Xiao-Dong

doi:10.1111/cns.12723

Cited by 18 publications

(16 citation statements)

References 41 publications

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“…EphrinB2 enhanced the TGF-β (Transforming Growth Factor-β) /Smad3 signaling-mediated cardiac fibrosis through regulating the interaction between Stat3 and Smad3 [ 15 ]. Interestingly, TGF-β also induced EphrinB2 expression in fibroblast, suggesting a positive feedback between EphrinB2 and TGF-β signaling [ 54 ]. Meanwhile, similar activation of EphrinB2 was observed in endothelial cells within TGF-β stimulation [ 55 ].…”

Section: Introductionmentioning

confidence: 99%

Essential roles of EphrinB2 in mammalian heart: from development to diseases

Xie

Zhang

et al. 2019

Cell Commun Signal

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EphrinB2, a membrane-tethered ligand preferentially binding to its receptor EphB4, is ubiquitously expressed in all mammals. Through the particular bidirectional signaling, EphrinB2 plays a critical role during the development of cardiovascular system, postnatal angiogenesis physiologically and pathologically, and cardiac remodeling after injuries as an emerging role. This review highlights the pivotal involvement of EphrinB2 in heart, from developmental cardiogenesis to pathological cardiac remodeling process. Further potential translational therapies will be discussed in targeting EphrinB2 signaling, to better understand the prevention and treatment of cardiovascular diseases.

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Section: Introductionmentioning

confidence: 99%

Essential roles of EphrinB2 in mammalian heart: from development to diseases

Xie

Zhang

et al. 2019

Cell Commun Signal

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Section: Neuroglial Cells As Potential Targets Of Rnai For Nerve Injumentioning

confidence: 99%

“…(i, i′) Addition of TGF-β1 and ephrin B2-targeting siRNA enhanced length of VSC4.1 axons as compared to TGF-β1 alone. Adapted with permission from Y Li et al 120 (B) Increased neurite outgrowth on/in conditioned media (CM) from chondroitin polymerizing factor (ChPF)-targeting siRNA-treated Neu7 astrocyte cell line. Cerebellar granule neurons were either grown on a combination of poly-L-lysine (PLL), laminin (LAM) and immobilized CM (a, c) in half DMEM and half neurobasal (NB) + B27 or on a combination of PLL and LAM in half NB + B27 and half CM from the Neu7 cells (b, d).…”

Section: Neuroglial Cells As Potential Targets Of Rnai For Nerve Injumentioning

confidence: 99%

“…Using a custom-made microfluidic platform containing chimeric ventral spinal cord 4.1 (VSC4.1) motoneurons, primary rat astrocytes and rat meningeal fibroblasts (MFb), they demonstrated that the administration of 30 nM of siRNA against ephrin-B2 complexed with SuperFectinTMII reagent (silencing efficiency ~84%) was able to ameliorate the effects of transforming growth factor-β1 (TGF-β1)induced astroglial-fibrotic scar formation and enhance axonal growth of VSC4.1 motoneurons (Figure 3). 120 Laabs et al targeted chondroitin polymerizing factor (ChPF), a key enzyme in the chondroitin sulphate proteoglycan (CSPG) biosynthetic pathway, in Neu7 cells (astrocytic cell line) using plasmids encoding shRNA through nucleofection (a method of transfecting nucleic acids into the cellular nucleus). Although the concentration of plasmids used was not stated, they were able to achieve up to 75% uptake efficiency and ~50% silencing efficiency, resulting in reduced CSPG glycosaminoglycans (GAGs) expression by Neu7 cells.…”

Section: Rnai In Astrocytesmentioning

confidence: 99%

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RNA interference in glial cells for nerve injury treatment

Lin

Kim

et al. 2020

J Tissue Eng

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Drivers of RNA interference are potent for manipulating gene and protein levels, which enable the restoration of dysregulated mRNA expression that is commonly associated with injuries and diseases. This review summarizes the potential of targeting neuroglial cells, using RNA interference, to treat nerve injuries sustained in the central nervous system. In addition, the various methods of delivering these RNA interference effectors will be discussed.

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“…In particular, the loss of neurons, for example, due to aging processes, stroke, or traumatic brain injury (TBI), is mostly irreversible. The function of the degenerating neurons can be partially compensated by neighboring neurons, but astroglial‐fibrotic scar formation minimizes neuronal regeneration (Li et al, ).…”

Section: Progesterone and Prsmentioning

confidence: 99%

Progesterone Effects in the Nervous System

Theis

Theiß

2019

The Anatomical Record

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The sex hormone progesterone is mainly known as a key factor in establishing and maintaining pregnancy. In addition, progesterone has been shown to induce morphological changes in the central and peripheral nervous system by increasing dendrito-, spino-, and synaptogenesis in Purkinje cells (Wessel et al.: Cell Mol Life Sci (2014a) 1723-1740 and increasing axonal outgrowth in dorsal root ganglia (Olbrich et al.: Endocrinology (2013) 3784-3795). These effects mediated mainly by the classical progesterone receptors (PRs) A and B seem to be limited to young neurons. It may be assumed that microRNAs (miRNAs), which are potent regulators of nervous system maturation and degeneration, are also involved in the regulation of progesterone-mediated neuronal plasticity by altering the expression patterns of the corresponding PR A/B receptors (Theis and Theiss: Neural Regen Res (2015) 547-549, Pieczora et al.: Cerebellum (2017) 376-387). This review critically discusses current data on the neuroprotective effect of progesterone and its corresponding receptors in the nervous system, with possible regulatory processes by miRNAs. Preclinical studies on stroke and traumatic brain injury revealed neuroprotective and neuroregenerative effects of progesterone in the treatment of severe neurological diseases in animal models, but have so far failed in humans. In this context, the identification of specific miRNAs that regulate the expression of progesterone and PR could help to exploit the neuroprotective potential of progesterone for the treatment of various neurological disorders. The human nervous system is a highly complex tissue composed of neurons and glial cells with a limited ability to regenerate after lesion or degeneration. In particular, the loss of neurons, for example, due to aging processes, stroke, or traumatic brain injury (TBI), is mostly irreversible. The function of the degenerating neurons can be partially compensated by neighboring neurons, but astroglial-fibrotic scar formation minimizes neuronal regeneration .Progesterone, a sexual hormone, is mainly known for its key role in the female reproductive circuit and the maintenance of pregnancy. In this context, the fact that progesterone is also expressed in the male organism is often neglected (Schumacher et al., 2014). Besides this, Abbreviations: BBB = blood brain barrier; CNS = central nervous system; DRG = dorsal root ganglia; GABA = Gamma-amino butyric acid; miRNA = microRNA; NMDAR = N-Methyl-D-aspartate receptor; PC = Purkinje cells; PGRMC1 = progesterone receptor membrane component 1; PNS = peripheral nervous system; PR = progesterone receptor; SCI = spinal cord injury; TBI = traumatic brain injury

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RNAi‐mediated ephrin‐B2 silencing attenuates astroglial‐fibrotic scar formation and improves spinal cord axon growth

Abstract: These results suggest that astroglial-fibrotic scar formation and particularly the expression of aggrecan and versican could be mitigated by ephrin-B2 specific siRNA, thus improving the microenvironment for spinal axon regeneration.

Cited by 18 publications

References 41 publications

Essential roles of EphrinB2 in mammalian heart: from development to diseases

Essential roles of EphrinB2 in mammalian heart: from development to diseases

RNA interference in glial cells for nerve injury treatment

Progesterone Effects in the Nervous System

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