Role of stress fibers and focal adhesions as a mediator for mechano-signal transduction in endothelial cells in situ

Kazuo Katoh, Yumiko Kano, Shigeo OokawaraDepartment of Anatomy, School of Medicine, Jichi Medical University, Yakushiji, Shimotsuke-city, Tochigi, JapanAbstract: Fluid shear stress is the mechanical force generated by the blood flow which is applied over the apical surface of endothelial cells in situ. The findings of a recent study suggest that stress fibers and its associated focal adhesions play roles in mechano-signal transduction mechanism. Stress fibers are present along the apical and the basal portion of the endothelial cells. Endothelial cells respond to fluid shear stress and change their morphological characteristics in both their cell shape and cytoskeletal organization. Atherosclerosis is a common disease of the arteries and it occurs in areas around the branching site of blood vessels where the cells are exposed to low fluid shear stress. The organization of stress fibers and focal adhesions are strongly influenced by shear stress, and therefore the generation of atherosclerotic lesions seem to be associated with the cytoskeletal components of endothelial cells. This review describes the possible role of the cytoskeleton as a mechano-transducer in endothelial cells in situ.Keywords: atherosclerosis, blood vessel, endothelial cell, cytoskeleton, stress fiber, focal adhesio

Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis-9

indicated in each panel. , Cerebral cortex showing Rip-positive oligodendrocytes () and neurofilament-positive axons (). The pial surface is at the top. , High-power photomicrographs of individual processes of Rip-positive oligodendrocytes () and neurofilament-positive axons () in the gray matter (layers II-III). In the cortex, immunoreactive cells for Rip, which possessed relatively thick and branched processes, were abundantly distributed in cortical layers II-VI, but were sparse in superficial molecular layer I. By contrast, Rip-positive cells in the cortex were significantly decreased in number throughout the cortex. , High-power views of individual Rip-positive cell in layers I-II. Rip-positive cells rats represent the typical morphology of myelinating oligodendrocytes, with round cell bodies and branched processes aligned in parallel (), whereas Rip-positive cells in rats frequently showed a morphological abnormality of distorted-shaped cell-bodies with fine and wavy processes that branched irregularly (). , Caudate-putamen of the basal ganglia immunostained for Rip () and neurofilament (). In the rat, Rip-positive oligodendrocytes exhibited an abnormal morphology with thinner and arborized processes, frequently accompanied by many spherical or granule-like fragments (). Extension of neurofilament-positive axons and axon bundles appeared normal in rats (). Scale bars: 50 μm (A-D); 20 μm (A'-D', E-K).<p><b>Copyright information:</b></p><p>Taken from "Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis"</p><p>http://www.biomedcentral.com/1471-2202/9/35</p><p>BMC Neuroscience 2008;9():35-35.</p><p>Published online 5 Apr 2008</p><p>PMCID:PMC2323389.</p><p></p

Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis-1

indicated in each panel. , Cerebral cortex showing Rip-positive oligodendrocytes () and neurofilament-positive axons (). The pial surface is at the top. , High-power photomicrographs of individual processes of Rip-positive oligodendrocytes () and neurofilament-positive axons () in the gray matter (layers II-III). In the cortex, immunoreactive cells for Rip, which possessed relatively thick and branched processes, were abundantly distributed in cortical layers II-VI, but were sparse in superficial molecular layer I. By contrast, Rip-positive cells in the cortex were significantly decreased in number throughout the cortex. , High-power views of individual Rip-positive cell in layers I-II. Rip-positive cells rats represent the typical morphology of myelinating oligodendrocytes, with round cell bodies and branched processes aligned in parallel (), whereas Rip-positive cells in rats frequently showed a morphological abnormality of distorted-shaped cell-bodies with fine and wavy processes that branched irregularly (). , Caudate-putamen of the basal ganglia immunostained for Rip () and neurofilament (). In the rat, Rip-positive oligodendrocytes exhibited an abnormal morphology with thinner and arborized processes, frequently accompanied by many spherical or granule-like fragments (). Extension of neurofilament-positive axons and axon bundles appeared normal in rats (). Scale bars: 50 μm (A-D); 20 μm (A'-D', E-K).<p><b>Copyright information:</b></p><p>Taken from "Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis"</p><p>http://www.biomedcentral.com/1471-2202/9/35</p><p>BMC Neuroscience 2008;9():35-35.</p><p>Published online 5 Apr 2008</p><p>PMCID:PMC2323389.</p><p></p

Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis-4

And rats. Insets show ferritin-positive cells in the substantia nigra reticulata. , Confocal images of double labeling for Rip and ferritin in the substantia nigra, showing the increased expression of ferritin in Rip-positive oligodendrocytes (). The diffuse immunoreactivity of ferritin was often observed around the Rip-positive oligodendrocytic processes (). Panels and represent pairs of double stained photomicrographs. Scale bars: 10 μm (A-D); 500 μm (E, F); 10 μm (insets in E, F); 10 μm (G-H'). , cerebellar white matter.<p><b>Copyright information:</b></p><p>Taken from "Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis"</p><p>http://www.biomedcentral.com/1471-2202/9/35</p><p>BMC Neuroscience 2008;9():35-35.</p><p>Published online 5 Apr 2008</p><p>PMCID:PMC2323389.</p><p></p

Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis-7

N and , respectively, showing the ED1-positive cells in the internal granule cell layer of the paraflocculus. indicates a capillary. , Choroid plexus in the lateral ventricles at P14. , Coronal sections through the aqueduct of the P14 brain. indicates the abnormal accumulation of ED1-positive cells underneath the ependymal layer and the formation of polyp-like protrusions into the aqueductal lumen. , Higher magnification of ED1-positive cells in the abnormal protrusion shown in . , Scanning confocal image of a transverse section of a blood vessel in the pons at P21, representing the ED1-positive cells () and vWF-positive endothelial cells (), with nuclear staining by TOPRO3 dye (). indicates the vascular lumen. , Confocal images of immunofluorescence labeling with ED1 () and Iba1 () across the vasculature in the P21 cerebellum. represent ED1-positive and Iba1-positive elongated cells found in the perivascular region. , Confocal images of immunostaining for ED1 () and Iba1 () through the section of the internal granular cell layer of the P21 cerebellum. indicate the ED1-positive and Iba1-positive ramified microglia. Panels and represent pairs of double-stained photomicrographs. Scale bars: 200 μm (A-D); 50 μm (E-H); 100 μm (I, J); 25 μm (K); 20 μm (L); 20 μm (M, N). ChP, choroid plexus; , cerebral aqueduct.<p><b>Copyright information:</b></p><p>Taken from "Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis"</p><p>http://www.biomedcentral.com/1471-2202/9/35</p><p>BMC Neuroscience 2008;9():35-35.</p><p>Published online 5 Apr 2008</p><p>PMCID:PMC2323389.</p><p></p

Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis-0

On of pons. A large number of Rip-positive promyelinating oligodendrocytes, which had a starburst morphology (), were observed in both the control () and (). , High-power photomicrographs of each promyelinating oligodendrocytes, respectively. The promyelinating oligodendrocyte () exhibited an oval cell body with multiple filopodia and a profuse network of processes, similar to those of wild-type (). , Reticular formation of pons. There were many Rip-positive myelinating oligodendrocytes ensheathing longitudinal axon bundles. , High-power photomicrographs of the myelinating oligodendrocyte in the control () or (). Each myelinating oligodendrocyte had the multiple linear processes arrays connected to the cell body by primary processes (), indicating that they had commenced axonal ensheathment. Scale bars: 100 μm (A, B); 20 μm (C, D); 100 μm (E, F); 20 μm (G, H).<p><b>Copyright information:</b></p><p>Taken from "Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis"</p><p>http://www.biomedcentral.com/1471-2202/9/35</p><p>BMC Neuroscience 2008;9():35-35.</p><p>Published online 5 Apr 2008</p><p>PMCID:PMC2323389.</p><p></p

Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis-10

Ocytes were distributed predominantly within the internal granule cell layer () and the white matter tracts in the cerebellum (), whereas Rip-positive processes of the mutant cerebellum were distorted and irregularly arranged, and sparsely distributed within the (). , Higher magnifications of the molecular layer (), Purkinje cell layer () and shown in A and B, respectively. The cerebellar oligodendrocytes in rats exhibited irregularly aligned short processes. , The number, density and distribution pattern of neurofilament-positive axons in cerebellar folia () were indistinguishable from those in the cerebellar folia (). Scale bars: 50 μm (A, B, C, D); 25 μm (A', B'). , internal granule cell layer; , molecular layer; , Purkinje cell layer.<p><b>Copyright information:</b></p><p>Taken from "Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis"</p><p>http://www.biomedcentral.com/1471-2202/9/35</p><p>BMC Neuroscience 2008;9():35-35.</p><p>Published online 5 Apr 2008</p><p>PMCID:PMC2323389.</p><p></p

Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis-5

Ence labeling of the subventricular zone (SVZ) surrounding the dorso-lateral corner of the lateral ventricle of wild-type rats, using antibodies against PDGFR-α () and atrn (). Atrn expression was not detected in PDGFR-α-positive cells (). , , Confocal images of the wild-type SVZ immunostained for A2B5 () and atrn (). Cell nuclei were visualized by TOPRO-3 staining (). show an enlarged view of the SVZ. Arrowhead depicts A2B5-positive but atrn-negative OPCs among the densely packed cells in the SVZ. , Atrn-positive cells (DAB, ) in the gray matter (layer V) of the adult cerebral neocortex. Atrn expression was observed in neurons including typical pyramidal neurons. , Atrn-positive cell (DAB, ) in the corpus callosum of the adult forebrain was indicated by . , , Confocal images of double immunofluorescent labeling with antibodies to atrn () and CNPase () in the adult cerebral cortex (layers II-III) () or the internal granule cell layer of the adult cerebellum (), respectively. Atrn expression was observed in many pyramidal or granule neurons, but not in CNPase-positive oligodendrocytes (). , , Immunohistochemical analysis for specificity of anti-atrn antibody in rat brain. Coronal sections through the adult cerebral cortex were immunostained with anti-atrn antibody. Atrn-immunoreactivity in wild-type SD () and () rats. Scale bars: 20 μm (A, B); 100 μm (C, D); 10 μm (E, F); 10 μm (F); 20 μm (G); 100 μm (I, J). , lateral ventricle.<p><b>Copyright information:</b></p><p>Taken from "Non-cell autonomous impairment of oligodendrocyte differentiation precedes CNS degeneration in the Zitter rat: Implications of macrophage/microglial activation in the pathogenesis"</p><p>http://www.biomedcentral.com/1471-2202/9/35</p><p>BMC Neuroscience 2008;9():35-35.</p><p>Published online 5 Apr 2008</p><p>PMCID:PMC2323389.</p><p></p