5 results on '"Laura, Korhonen"'
Search Results
2. Hepatocyte growth factor activator inhibitor-1 is induced by bone morphogenetic proteins and regulates proliferation and cell fate of neural progenitor cells.
- Author
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Raili Koivuniemi, Johanna Mäkelä, Marie-Estelle Hokkanen, Céline Bruelle, Tho Huu Ho, Roxana Ola, Laura Korhonen, Jim Schröder, Hiroaki Kataoka, and Dan Lindholm
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Neural progenitor cells (NPCs) in the developing neuroepithelium are regulated by intrinsic and extrinsic factors. There is evidence that NPCs form a self-supporting niche for cell maintenance and proliferation. However, molecular interactions and cell-cell contacts and the microenvironment within the neuroepithelium are largely unknown. We hypothesized that cellular proteases especially those associated with the cell surface of NPCs play a role in regulation of progenitor cells in the brain. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we show that NPCs, isolated from striatal anlage of developing rat brain, express hepatocyte growth factor activator inhibitor-1 and -2 (HAI-1 and HAI-2) that are cell surface-linked serine protease inhibitors. In addition, radial glia cells derived from mouse embryonic stem cells also express HAI-1 and HAI-2. To study the functional significance of HAI-1 and HAI-2 in progenitor cells, we modulated their levels using expression plasmids or silencing RNA (siRNA) transfected into the NPCs. Data showed that overexpression of HAI-1 or HAI-2 decreased cell proliferation of cultured NPCs, whilst their siRNAs had opposite effects. HAI-1 also influenced NPC differentiation by increasing the number of glial fibrillary acidic protein (GFAP) expressing cells in the culture. Expression of HAI-1 in vivo decreased cell proliferation in developing neuroepithelium in E15 old animals and promoted astrocyte cell differentiation in neonatal animals. Studying the regulation of HAI-1, we observed that Bone morphogenetic protein-2 (BMP-2) and BMP-4 increased HAI-1 levels in the NPCs. Experiments using HAI-1-siRNA showed that these BMPs act on the NPCs partly in a HAI-1-dependent manner. CONCLUSIONS: This study shows that the cell-surface serine protease inhibitors, HAI-1 and HAI-2 influence proliferation and cell fate of NPCs and their expression levels are linked to BMP signaling. Modulation of the levels and actions of HAI-1 in NPCs may be of a potential value in stem cell therapies in various brain diseases.
- Published
- 2013
- Full Text
- View/download PDF
3. Interferon-gamma produced by microglia and the neuropeptide PACAP have opposite effects on the viability of neural progenitor cells.
- Author
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Johanna Mäkelä, Raili Koivuniemi, Laura Korhonen, and Dan Lindholm
- Subjects
Medicine ,Science - Abstract
Inflammation is part of many neurological disorders and immune reactions may influence neuronal progenitor cells (NPCs) contributing to the disease process. Our knowledge about the interplay between different cell types in brain inflammation are not fully understood. It is important to know the mechanisms and factors involved in order to enhance regeneration and brain repair. We show here that NPCs express receptors for interferon-gamma (IFNgamma), and IFNgamma activates the signal transducer and activator of transcription (STAT) protein-1. IFNgamma reduced cell proliferation in NPCs by upregulation of the cell cycle protein p21 as well as induced cell death of NPCs by activating caspase-3. Studies of putative factors for rescue showed that the neuropeptide, Pituitary adenylate cyclase-activating polypeptide (PACAP) increased cell viability, the levels of p-Bad and reduced caspase-3 activation in the NPCs. Medium from cultured microglia contained IFNgamma and decreased the viability of NPCs, whilst blocking with anti-IFNgamma antibodies counteracted this effect. The results show that NPCs are negatively influenced by IFNgamma whereas PACAP is able to modulate its action. The interplay between IFNgamma released from immune cells and PACAP is of importance in brain inflammation and may affect the regeneration and recruitment of NPCs in immune diseases. The observed effects of IFNgamma on NPCs deserve to be taken into account in human anti-viral therapies particularly in children with higher rates of brain stem cell proliferation.
- Published
- 2010
- Full Text
- View/download PDF
4. Interferon-gamma produced by microglia and the neuropeptide PACAP have opposite effects on the viability of neural progenitor cells
- Author
-
Raili Koivuniemi, Laura Korhonen, Dan Lindholm, Johanna Mäkelä, and Medicum
- Subjects
Cell Biology/Cell Growth and Division ,lcsh:Medicine ,Cell Biology/Cell Signaling ,0302 clinical medicine ,311 Basic medicine ,Phosphorylation ,lcsh:Science ,Neurons ,0303 health sciences ,Multidisciplinary ,Microglia ,Stem Cells ,Neurogenesis ,PROLIFERATION ,DEATH ,Cell Biology/Cellular Death and Stress Responses ,Neural stem cell ,Developmental Biology/Stem Cells ,3. Good health ,Cell biology ,STAT1 Transcription Factor ,medicine.anatomical_structure ,Pituitary Adenylate Cyclase-Activating Polypeptide ,Stem cell ,Neuroscience/Neurobiology of Disease and Regeneration ,STEM-CELLS ,Research Article ,GROWTH-FACTOR ,ACTIVATING POLYPEPTIDE PACAP ,Biology ,RAT-BRAIN ,NEUROGENESIS ,Interferon-gamma ,VASOACTIVE-INTESTINAL-PEPTIDE ,03 medical and health sciences ,Neuroscience/Neuronal Signaling Mechanisms ,medicine ,otorhinolaryngologic diseases ,Animals ,Viability assay ,Progenitor cell ,Cell Biology/Gene Expression ,Cell Proliferation ,Neurological Disorders/Infectious Diseases of the Nervous System ,030304 developmental biology ,Cell growth ,CENTRAL-NERVOUS-SYSTEM ,lcsh:R ,IN-VITRO ,Neurological Disorders/Neuroendocrinology and Pituitary ,Rats ,Developmental Biology/Neurodevelopment ,stomatognathic diseases ,Immunology ,Developmental Biology/Cell Differentiation ,STAT protein ,lcsh:Q ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Inflammation is part of many neurological disorders and immune reactions may influence neuronal progenitor cells (NPCs) contributing to the disease process. Our knowledge about the interplay between different cell types in brain inflammation are not fully understood. It is important to know the mechanisms and factors involved in order to enhance regeneration and brain repair. We show here that NPCs express receptors for interferon-gamma (IFNgamma), and IFNgamma activates the signal transducer and activator of transcription (STAT) protein-1. IFNgamma reduced cell proliferation in NPCs by upregulation of the cell cycle protein p21 as well as induced cell death of NPCs by activating caspase-3. Studies of putative factors for rescue showed that the neuropeptide, Pituitary adenylate cyclase-activating polypeptide (PACAP) increased cell viability, the levels of p-Bad and reduced caspase-3 activation in the NPCs. Medium from cultured microglia contained IFNgamma and decreased the viability of NPCs, whilst blocking with anti-IFNgamma antibodies counteracted this effect. The results show that NPCs are negatively influenced by IFNgamma whereas PACAP is able to modulate its action. The interplay between IFNgamma released from immune cells and PACAP is of importance in brain inflammation and may affect the regeneration and recruitment of NPCs in immune diseases. The observed effects of IFNgamma on NPCs deserve to be taken into account in human anti-viral therapies particularly in children with higher rates of brain stem cell proliferation.
- Published
- 2010
5. Hepatocyte Growth Factor Activator Inhibitor-1 Is Induced by Bone Morphogenetic Proteins and Regulates Proliferation and Cell Fate of Neural Progenitor Cells
- Author
-
Roxana Ola, Raili Koivuniemi, Marie-Estelle Hokkanen, Tho Huu Ho, Johanna Mäkelä, Hiroaki Kataoka, Jim Schröder, Dan Lindholm, Laura Korhonen, Céline Bruelle, Medicum, Department of Biochemistry and Developmental Biology, and Neuroscience Center
- Subjects
Cellular differentiation ,Neuroepithelial Cells ,lcsh:Medicine ,Bone Morphogenetic Protein 2 ,Bone Morphogenetic Protein 4 ,TUMOR-SUPPRESSOR GENE ,ADULT NEUROGENESIS ,Biochemistry ,Cell Fate Determination ,Mice ,0302 clinical medicine ,Neural Stem Cells ,Phosphorylation ,lcsh:Science ,Mitogen-Activated Protein Kinase 1 ,0303 health sciences ,Membrane Glycoproteins ,Mitogen-Activated Protein Kinase 3 ,Multidisciplinary ,Neurogenesis ,virus diseases ,Cell Differentiation ,Neural stem cell ,Cell biology ,Neuroepithelial cell ,Stem cell ,STEM-CELLS ,Neuroglia ,Research Article ,TYPE-1 HAI-1 ,NEURONAL DIFFERENTIATION ,animal structures ,education ,Biology ,Cell fate determination ,TUBE CLOSURE ,Signaling Pathways ,RAT HIPPOCAMPUS ,03 medical and health sciences ,Developmental Neuroscience ,Growth Factors ,Neuroglial Development ,Animals ,Humans ,SERINE-PROTEASE INHIBITOR ,Rats, Wistar ,Progenitor cell ,Cell Proliferation ,030304 developmental biology ,GLIOBLASTOMA CELLS ,lcsh:R ,KUNITZ DOMAINS ,Proteins ,Bone Morphogenetic Protein Receptors ,Embryonic stem cell ,Rats ,Transmembrane Proteins ,Gene Expression Regulation ,lcsh:Q ,3111 Biomedicine ,Molecular Neuroscience ,030217 neurology & neurosurgery ,Developmental Biology ,Neuroscience - Abstract
Background Neural progenitor cells (NPCs) in the developing neuroepithelium are regulated by intrinsic and extrinsic factors. There is evidence that NPCs form a self-supporting niche for cell maintenance and proliferation. However, molecular interactions and cell-cell contacts and the microenvironment within the neuroepithelium are largely unknown. We hypothesized that cellular proteases especially those associated with the cell surface of NPCs play a role in regulation of progenitor cells in the brain. Methodology/Principal Findings In this work, we show that NPCs, isolated from striatal anlage of developing rat brain, express hepatocyte growth factor activator inhibitor-1 and -2 (HAI-1 and HAI-2) that are cell surface-linked serine protease inhibitors. In addition, radial glia cells derived from mouse embryonic stem cells also express HAI-1 and HAI-2. To study the functional significance of HAI-1 and HAI-2 in progenitor cells, we modulated their levels using expression plasmids or silencing RNA (siRNA) transfected into the NPCs. Data showed that overexpression of HAI-1 or HAI-2 decreased cell proliferation of cultured NPCs, whilst their siRNAs had opposite effects. HAI-1 also influenced NPC differentiation by increasing the number of glial fibrillary acidic protein (GFAP) expressing cells in the culture. Expression of HAI-1 in vivo decreased cell proliferation in developing neuroepithelium in E15 old animals and promoted astrocyte cell differentiation in neonatal animals. Studying the regulation of HAI-1, we observed that Bone morphogenetic protein-2 (BMP-2) and BMP-4 increased HAI-1 levels in the NPCs. Experiments using HAI-1-siRNA showed that these BMPs act on the NPCs partly in a HAI-1-dependent manner. Conclusions This study shows that the cell-surface serine protease inhibitors, HAI-1 and HAI-2 influence proliferation and cell fate of NPCs and their expression levels are linked to BMP signaling. Modulation of the levels and actions of HAI-1 in NPCs may be of a potential value in stem cell therapies in various brain diseases.
- Published
- 2013
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