Differential regulation of osteopontin receptors, CD44 and the αv and β3 integrin subunits, in the rat hippocampus following transient forebrain ischemia

Kang, Woojin; Choi, Jeong-Sun; Shin, Yoo-Jin; Kim, Ha-Young; Cha, Jung-Ho; Lee, Ji-Yeon; Chun, Myung-Hoon; Lee, Mun‐Yong

doi:10.1016/j.brainres.2008.06.106

Cited by 32 publications

(28 citation statements)

References 34 publications

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“…These dotted OPN patterns increased on days 3-14 after reperfusion and thereafter decreased gradually, but the expression was sustained for more than 4 weeks. In support of our results, several studies have reported punctate OPN immunoreactivity in the extracellular matrix following brain injury including ischemia (Borges et al, 2008;Choi et al, 2007;Ellison et al, 1998;Kang et al, 2008;Yan et al, 2009). Here, we found that OPN-immunoreactive dots were indeed small flakes, irregular in shape and size and occasionally containing degenerated mitochondria by EM observations.…”

Section: Discussionsupporting

confidence: 90%

Osteopontin: Correlation with phagocytosis by brain macrophages in a rat model of stroke

Shin

Kim

Choi

et al. 2010

Glia

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Osteopontin (OPN) is an adhesive glycoprotein linked to a variety of pathophysiological processes. We investigated whether OPN might act as an opsonin in the diseased brain by studying the postischemic expression and localization of OPN mRNA and protein in a rat model of ischemic stroke. In addition, we characterized the subcellular localization of OPN protein in the ischemic brain core. Induction of OPN mRNA occurred in activated microglia/macrophages in the ischemic core on days 3-7 after reperfusion and this was sustained up to day 28, at least. OPN protein was synthesized and secreted by brain macrophages, which first surrounded damaged striatal white matter tracts and then infiltrated into them. Punctate OPN-immunoreactive profiles were scattered throughout the infarction core except in white matter bundles. Electron microscopy showed the localization of OPN protein along the membranes lining what appeared to be the debris of dead neurons. These were located in the extracellular space and within the cytoplasm of brain macrophages, indicating that the OPN protein accumulated selectively on the surface of dead cells, most of which were phagocytosed subsequently by brain macrophages. However, no significant induction of OPN occurred in degenerating striatal white matter tracts or in brain macrophage-engulfed axonic or myelin debris. These data suggest that OPN secreted by brain macrophages in this rat model of stroke might be involved in the phagocytosis of fragmented cell debris and possibly not in the phagocytosis of axonic or myelin debris.

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Section: Discussionsupporting

confidence: 90%

Osteopontin: Correlation with phagocytosis by brain macrophages in a rat model of stroke

Shin

Kim

Choi

et al. 2010

Glia

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“…These observations suggest that integrin-b1 activation is involved in the movement of micoglial cell bodies and that the cell migration requires activation of other signaling pathways in addition to those underlying the process extension. Integrin-b has been reported to be upregulated by activated microglia in pathological states, such as nerve injury or ischemia, (Kang et al, 2008;Kloss et al, 1999). Expression of ECM ligands for integrin-b1 is increased in pathological states, and fibronectin leak to brain parenchyma from blood vessels when blood-brain-barrier is damaged by some pathological conditions (Liesi et al, 1984;Nasu-Tada et al, 2006;Tate et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

P2Y₁₂ receptor‐mediated integrin‐β1 activation regulates microglial process extension induced by ATP

Ohsawa

Irino

Sanagi

et al. 2010

Glia

111

105

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Microglia are the primary immune surveillance cells in the brain, and when activated they play critical roles in inflammatory reactions and tissue repair in the damaged brain. Microglia rapidly extend their processes toward the damaged areas in response to stimulation of the metabotropic ATP receptor P2Y(12) by ATP released from damaged tissue. This chemotactic response is a highly important step that enables microglia to function properly at normal and pathological sites in the brain. To investigate the molecular pathways that underlie microglial process extension, we developed a novel method of modeling microglial process extension that uses transwell chambers in which the insert membrane is coated with collagen gel. In this study, we showed that ATP increased microglial adhesion to collagen gel, and that the ATP-induced process extension and increase in microglial adhesion were inhibited by integrin blocking peptides, RGD, and a functional blocking antibody against integrin-beta1. An immunoprecipitation analysis with an antibody against the active form of integrin-beta1 showed that P2Y(12) mediated the integrin-beta1 activation by ATP. In addition, time-lapse imaging of EGFP-labeled microglia in mice hippocampal slices showed that RGD inhibited the directional process extension toward the nucleotide source, and immunohistochemical staining showed that integrin-beta1 accumulated in the tips of the microglial processes in rat hippocampal slices stimulated with ADP. These findings indicate that ATP induces the integrin-beta1 activation in microglia through P2Y(12) and suggest that the integrin-beta1 activation is involved in the directional process extension by microglia in brain tissue.

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“…It also carries out signal transduction via a vinculin-involved focal adhesion complex (Samanna et al, 2006). One of its ligands (Chellaiah and Hruska, 2003;Miyauchi et al, 2006;Samanna et al, 2006), OPN, can interact with the cell surface receptor, CD44 (Chellaiah and Hruska, 2003;Weber et al, 1996), which also links ECM proteins and the cytoskeleton (Kang et al, 2008). Fluid flow induced OPN upregulation in MC3T3-E1 cells has also been found (Ponik et al, 2007;You et al, 2001).…”

Section: Integrin-associated Molecules Expression At Mrna Levelmentioning

confidence: 99%

Oscillatory fluid flow elicits changes in morphology, cytoskeleton and integrin-associated molecules in MLO-Y4 cells, but not in MC3T3-E1 cells

Zhang

et al. 2012

Biol. Res.

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Interstitial fl uid fl ow stress is one of the most important mechanical stimulations of bone cells under physiological conditions. Osteocytes and osteoblasts act as primary mechanosensors within bones, and in vitro are able to respond to fl uid shear stress, both morphologically and functionally. However, there is little information about the response of integrin-associated molecules using both osteoblasts and osteocytes. In this study, we investigated the changes in response to 2 hours of oscillatory fl uid fl ow stress in the MLO-Y4 osteocyte-like cell line and the MC3T3-E1 osteoblast-like cell line. MLO-Y4 cells exhibited a signifi cant increase in the expression of integrin-associated molecules, including OPN, CD44, vinculin and integrin αvβ3. However, there was no or limited increase observed in MC3T3-E1 osteoblast-like cells. Cell area and fi ber stress formation were also markedly promoted by fl uid fl ow only in MLO-Y4 cells. But the numbers of processes per cell remain unaff ected in both cell lines.

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Differential regulation of osteopontin receptors, CD44 and the αv and β3 integrin subunits, in the rat hippocampus following transient forebrain ischemia

Cited by 32 publications

References 34 publications

Osteopontin: Correlation with phagocytosis by brain macrophages in a rat model of stroke

Osteopontin: Correlation with phagocytosis by brain macrophages in a rat model of stroke

P2Y₁₂ receptor‐mediated integrin‐β1 activation regulates microglial process extension induced by ATP

Oscillatory fluid flow elicits changes in morphology, cytoskeleton and integrin-associated molecules in MLO-Y4 cells, but not in MC3T3-E1 cells

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Differential regulation of osteopontin receptors, CD44 and the αv and β3 integrin subunits, in the rat hippocampus following transient forebrain ischemia

Cited by 32 publications

References 34 publications

Osteopontin: Correlation with phagocytosis by brain macrophages in a rat model of stroke

Osteopontin: Correlation with phagocytosis by brain macrophages in a rat model of stroke

P2Y12 receptor‐mediated integrin‐β1 activation regulates microglial process extension induced by ATP

Oscillatory fluid flow elicits changes in morphology, cytoskeleton and integrin-associated molecules in MLO-Y4 cells, but not in MC3T3-E1 cells

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P2Y₁₂ receptor‐mediated integrin‐β1 activation regulates microglial process extension induced by ATP