CD44 expression in astrocytes and microglia is associated with ALS progression in a mouse model

Matsumoto, Tomohiro; Imagama, Shiro; Hirano, Ken‐ichi; Ohgomori, Tomohiro; Natori, Takahiro; Kobayashi, Kazuyoshi; Muramoto, Akio; Ishiguro, Naoki; Kadomatsu, Kenji

doi:10.1016/j.neulet.2012.05.048

Cited by 52 publications

(50 citation statements)

References 26 publications

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“…In some human disease, CD44 expression was reported in astrocyte-restricted precursor cells or reactive astrocytes [3,23]. On the other hand, CD44 expression both in the microglia and astrocytes has been also reported [13]. The discrepancy between the results obtained here and those …”

Section: Discussioncontrasting

confidence: 86%

“…In a study using SOD1G93A mice [13], CD44 was expressed in most activated astrocytes and in a portion of activated microglia during ALS progression whereas CD44 was hardly detected in wild type mice. When primary cultured microglia from WT mice were exposed to LPS and IFN-gamma, CD44 was induced in microglia, whereas cultured astrocytes from WT mice produced CD44 even without stimulation, but they produced more CD44 with stimulation [13]. These suggest that interaction between CD44 and its ligand promotes glial cell migration and their accumulation in lesion sites.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have showed that upregulation of CD44 expression after brain injury such as ischemia [10,11] and brain traumas [12]. In inflammatory conditions CD44 have been suggested to play a role in endothelial cell recognition, migration of inflammatory cells, cell-matrix interactions, and regulation of cytokine expression [11,13]. After ischemic brain injury of the rat, CD44 was induced in microglia and a subset of macrophage while basal expression of CD44 was localized primarily in the area of microvessel [10].…”

Section: Introductionmentioning

confidence: 99%

“…After ischemic brain injury of the rat, CD44 was induced in microglia and a subset of macrophage while basal expression of CD44 was localized primarily in the area of microvessel [10]. In a study using SOD1G93A mice [13], CD44 was expressed in most activated astrocytes and in a portion of activated microglia during ALS progression whereas CD44 was hardly detected in wild type mice. When primary cultured microglia from WT mice were exposed to LPS and IFN-gamma, CD44 was induced in microglia, whereas cultured astrocytes from WT mice produced CD44 even without stimulation, but they produced more CD44 with stimulation [13].…”

Section: Introductionmentioning

confidence: 99%

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CD44 Expression in Microglia of the Retina and Cerebellum of Developing and Adult Chicken

Kim

Sohn

Seo

et al. 2017

Korean J Phys Anthropol

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: CD44 is a transmembrane protein that acts as a receptor for an adhesion molecule, hyaluronic acid. The type of cells expressing CD44 and roles of CD44 are still controversial and need to be elucidated. The aim of the present study was to examine the type of cells expressing CD44 and the changes in their distribution in the retina and the cerebellum of the developing and adult chicken. Embryonic day 14 (E14) and post-hatch day 90 (P90) chickens were used in this study. CD44-immunoreactive (ir) cells were observed both in the retina and the cerebellum of the two developmental stages examined. In the retina of E14, CD44-ir cells were mainly located in the nerve fiber layer. In adults, most of the CD44-ir cells were in the nerve fiber layer and some were dispersed in other layers of the retina. In the cerebellum of E14, CD44-ir cells were distributed throughout the cerebellar cortex, including the external and internal granular layers. CD44-ir cells were more frequently found in the cerebellum of P90 adult chickens than in that of E14 embryos. At higher magnification, CD44-ir cells showed ramified cytoplasmic processes irradiating from their cell bodies. In the retina and in the cerebellum of all ages examined, double staining showed that most of the CD44-ir cells also expressed RCA-1, a marker of microglia. In contrast to that, at the same locations, GFAP and CD44 were not co-expressed in cells. When the adult retina was stimulated by LPS, CD44 immunoreactivity increased, and CD44-ir cells were also RCA-1-positive. The present results indicated that CD44 was expressed in microglia of the retina and the cerebellum of the developing and adult chicken even in normal conditions, and microglial CD44 expression was increased upon LPS stimulation.

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Section: Discussioncontrasting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD44 Expression in Microglia of the Retina and Cerebellum of Developing and Adult Chicken

Kim

Sohn

Seo

et al. 2017

Korean J Phys Anthropol

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“…Hyaluronans bound to CD44 are catabolized in lysosomes (86). Although the mechanism of CD44 turnover in TBI has yet to be fully understood, cytokines, CD44 phosphorylation and induction of alternatively spliced isoforms of CD44 could be involved in the removal of degraded hyaluronan products (39, 40, 64, 85, 87–93). …”

Section: Discussionmentioning

confidence: 99%

Divergent Temporal Expression of Hyaluronan Metabolizing Enzymes and Receptors with Craniotomy vs. Controlled-Cortical Impact Injury in Rat Brain: A Pilot Study

2014

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Traumatic brain injury (TBI) triggers many secondary changes in tissue biology, which ultimately determine the extent of injury and clinical outcome. Hyaluronan [hyaluronic acid (HA)] is a protective cementing gel present in the intercellular spaces whose degradation has been reported as a causative factor in tissue damage. Yet little is known about the expression and activities of genes involved in HA catabolism after TBI. Young adult male Sprague-Dawley rats were assigned to three groups: naïve control, craniotomy, and controlled-cortical impact-induced TBI (CCI-TBI). Four animals per group were sacrificed at 4 h, 1, 3, and 7 days post-CCI. The mRNA expression of hyaluronan synthases (HAS1-3), hyaluronidases (enzymes for HA degradation, HYAL 1–4, and PH20), and CD44 and RHAMM (membrane receptors for HA signaling and removal) were determined using real-time PCR. Compared to the naïve controls, expression of HAS1 and HAS2 mRNA, but not HAS3 mRNA increased significantly following craniotomy alone and following CCI with differential kinetics. Expression of HAS2 mRNA increased significantly in the ipsilateral brain at 1 and 3 days post-CCI. HYAL1 mRNA expression also increased significantly in the craniotomy group and in the contralateral CCI at 1 and 3 days post-CCI. CD44 mRNA expression increased significantly in the ipsilateral CCI at 4 h, 1, 3, and 7 days post-CCI (up to 25-fold increase). These data suggest a dynamic regulation and role for HA metabolism in secondary responses to TBI.

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Association of serum Spp1 levels with disease progression in ALS and SBMA

Ju,

Ban,

et al. 2024

Ann Clin Transl Neurol

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ObjectiveIn comparison with amyotrophic lateral sclerosis (ALS), the contribution of neuroinflammation in spinobulbar muscular atrophy (SBMA) has been less explored. We investigated the role of neuroinflammation in the pathogenesis of ALS and SBMA by analyzing systemic inflammatory markers and osteopontin (Spp1).MethodsThis study involved 105 ALS, 77 SBMA, and 55 healthy controls. We measured their systemic inflammatory markers, serum Spp1, and cytokine levels (interferon‐γ, interleukin [IL]‐1β, IL‐6, IL‐8, IL‐10, tumor necrosis factor‐α, and IL‐17A), investigated correlations between Spp1 levels and clinical features, and evaluated ALS survival rates according to Spp1 levels.ResultsIn the ALS group, systemic inflammatory markers were significantly higher than in the control and SBMA groups. Spp1 levels were observed to be higher in ALS patients, but the difference was not statistically significant among the study groups. Cytokine profiles were comparable. In ALS, higher Spp1 levels were correlated with lower ALS Functional Rating Scale‐Revised (ALSFRS‐R) scores (r = −0.25, p = 0.02) and faster disease progression rate (r = 0.37, p < 0.001). After adjusting for other prognostic indicators, high Spp1 levels were independently associated with shorter survival in ALS patients (hazard ratio 13.65, 95% confidence interval 2.57–72.53, p < 0.01).InterpretationNeuroinflammation does not appear to be a primary contributor to the pathogenesis of SBMA. Serum Spp1 levels may serve as a reliable biomarker for disease progression and prognosis in ALS. These findings expand our understanding of these two distinct motor neuron disorders and offer a potential biomarker for future studies.

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CD44 expression in astrocytes and microglia is associated with ALS progression in a mouse model

Cited by 52 publications

References 26 publications

CD44 Expression in Microglia of the Retina and Cerebellum of Developing and Adult Chicken

CD44 Expression in Microglia of the Retina and Cerebellum of Developing and Adult Chicken

Divergent Temporal Expression of Hyaluronan Metabolizing Enzymes and Receptors with Craniotomy vs. Controlled-Cortical Impact Injury in Rat Brain: A Pilot Study

Association of serum Spp1 levels with disease progression in ALS and SBMA

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