ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2011
Multipotent mesenchymal stromal cells increase tPA expression and concomitantly decrease PAI-1 expression in astrocytes through the sonic hedgehog signaling pathway after stroke (in vitro study).
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator.Journal of personalized medicine · 2023Review
- Plasminogen Activators in Neurovascular and Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- The Neuroprotective Roles of Sonic Hedgehog Signaling Pathway in Ischemic Stroke.Neurochemical research · 2018Review
- Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC).Stem cell research & therapy · 2017Article
- Stem Cell Recipes of Bone Marrow and Fish: Just What the Stroke Doctors Ordered.Stem cell reviews and reports · 2017Review
- Article
- Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke.Progress in neurobiology · 2016Review
- Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles.International journal of molecular sciences · 2016Review
- The Plasminogen Activation System Promotes Dendritic Spine Recovery and Improvement in Neurological Function After an Ischemic Stroke.Translational stroke research · 2016Article
- Mesenchymal Stromal Cells Promote Axonal Outgrowth Alone and Synergistically with Astrocytes via tPA.PloS one · 2016Article
- The Role of TLR4 and Fyn Interaction on Lipopolysaccharide-Stimulated PAI-1 Expression in Astrocytes.Molecular neurobiology · 2015Article
- Update on therapeutic mechanism for bone marrow stromal cells in ischemic stroke.Journal of molecular neuroscience : MN · 2014Review
- Article
- Novel siRNA delivery strategy: a new "strand" in CNS translational medicine?Cellular and molecular life sciences : CMLS · 2014Review
- Review
- Plasminogen deficiency causes reduced corticospinal axonal plasticity and functional recovery after stroke in mice.PloS one · 2014Article
- Exosomes/miRNAs as mediating cell-based therapy of stroke.Frontiers in cellular neuroscience · 2014Review
- Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Review
- The sonic hedgehog pathway mediates brain plasticity and subsequent functional recovery after bone marrow stromal cell treatment of stroke in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Multipotent mesenchymal stromal cells decrease transforming growth factor β1 expression in microglia/macrophages and down-regulate plasminogen activator inhibitor 1 expression in astrocytes after stroke.Neuroscience letters · 2013Article
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Authors and funding
8 authors at 2 institutions in 1 country.
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Abstract
Multipotent mesenchymal stromal cells (MSCs) increase tissue plasminogen activator (tPA) activity in astrocytes of the ischemic boundary zone, leading to increased neurite outgrowth in the brain. To probe the mechanisms that underlie MSC-mediated activation of tPA, we investigated the morphogenetic gene, sonic hedgehog (Shh) pathway. In vitro oxygen and glucose deprivation and coculture of astrocytes and MSCs were used to mimic an in vivo ischemic condition. Both real-time-PCR and western blot showed that MSC coculture significantly increased the Shh level and concomitantly increased tPA and decreased plasminogen activator inhibitor 1 (PAI-1) levels in astrocytes. Inhibiting the Shh signaling pathway with cyclopamine blocked the increase of tPA and the decrease of PAI-1 expression in astrocytes subjected to MSC coculture or recombinant mouse Shh (rm-Shh) treatment. Both MSCs and rm-Shh decreased the transforming growth factor-β1 level in astrocytes, and the Shh pathway inhibitor cyclopamine reversed these decreases. Both Shh-small-interfering RNA (siRNA) and Glil-siRNA downregulated Shh and Gli1 (a key mediator of the Shh transduction pathway) expression in cultured astrocytes and concomitantly decreased tPA expression and increased PAI-1 expression in these astrocytes after MSC or rm-Shh treatment. Our data indicate that MSCs increase astrocytic Shh, which subsequently increases tPA expression and decreases PAI-1 expression after ischemia.
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Registered trials
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