ArticleStem cell research & therapy2018
DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 14 citations in OpenAlex.
- DNA Topoisomerase IIβ Suppresses Microglial Inflammatory Cytokine Release: A Potential Regulator of Neuroinflammation.Neurochemical research · 2026Article
- Molecular links between reelin downregulation, topoisomerase IIβ alterations, and proteins involved in Alzheimer pathology in human SH-SY5Y neuroblastoma cell line.Experimental brain research · 2026Article
- A53T α-Synuclein Expression is Associated with Altered Dopaminergic-Like Differentiation and Reduced DNA Topoisomerase IIβ Levels in an In Vitro Model of Parkinson's Disease.Molecular neurobiology · 2026Article
- Early α-Synuclein Pathology Induces Neuroinflammation and Decreases Topoisomerase IIβ Expression in A53T Mice.Inflammation · 2025Article
- 9-Methylfascaplysin, a Marine-Derived Bioactive Compound, Promotes Neurite Outgrowth via the Inhibition of ROCK2.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Topoisomerase II Inhibition in Cancer: A Focus on Metal Complexes.Mini reviews in medicinal chemistry · 2025Review
- TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.Molecular neurobiology · 2022Article
- Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons.International journal of molecular sciences · 2022Review
- ROCK2 Promotes Osteosarcoma Growth and Glycolysis by Up-Regulating HKII via Phospho-PI3K/AKT Signalling.Cancer management and research · 2021Article
- Molecular Mechanisms Involved in Neural Substructure Development during Phosphodiesterase Inhibitor Treatment of Mesenchymal Stem Cells.International journal of molecular sciences · 2020Article
- Actin Alpha 2 (ACTA2) Downregulation Inhibits Neural Stem Cell Migration through Rho GTPase Activation.Stem cells international · 2020Article
- TOP2B: The First Thirty Years.International journal of molecular sciences · 2018Review
- The Roles of DNA Topoisomerase IIβ in Transcription.International journal of molecular sciences · 2018Review
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2 authors at 1 institution in 1 country.
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Abstract
backgroundDNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. METHODS AND
resultsFor this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ.
conclusionOur results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.
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