Transforming growth factor-β1 upregulates keratan sulfate and chondroitin sulfate biosynthesis in microglias after brain injury

Yin, Jian; Sakamoto, Kazunari; Zhang, Haoqian; Ito, Zenya; Imagama, Shiro; Kishida, Satoshi; Natori, Takahiro; Sawada, Makoto; Matsuyama, Yukihiro

doi:10.1016/j.brainres.2009.01.042

Cited by 28 publications

(26 citation statements)

References 53 publications

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“…We also found that a portion of the Iba1-positive cells were also KS positive at 3 d, a time point at which most of the Iba1-positive cells were expected to be resident microglia, not macrophages (data not shown). Consistent with this, we have recently reported that primary cultured microglia express KS, and this expression is enhanced by TGF-␤, a microglia-activating cytokine usually induced after neuronal injuries (Yin et al, 2009). Considering these results together, it is most likely that, in addition to oligodendrocyte precursor cells (PDGFr positive), activated microglia are a main source of KSPG.…”

Section: Discussionsupporting

confidence: 77%

N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

Ito¹,

Sakamoto²,

Imagama³

et al. 2010

J. Neurosci.

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Neurons in the adult CNS do not spontaneously regenerate after injuries. The glycosaminoglycan keratan sulfate is induced after spinal cord injury, but its biological significance is not well understood. Here we investigated the role of keratan sulfate in functional recovery after spinal cord injury, using mice deficient in N-acetylglucosamine 6-O-sulfotransferase-1 that lack 5D4-reactive keratan sulfate in the CNS. We made contusion injuries at the 10th thoracic level. Expressions of N-acetylglucosamine 6-O-sulfotransferase-1 and keratan sulfate were induced after injury in wild-type mice, but not in the deficient mice. The wild-type and deficient mice showed similar degrees of chondroitin sulfate induction and of CD11b-positive inflammatory cell recruitment. However, motor function recovery, as assessed by the footfall test, footprint test, and Basso mouse scale locomotor scoring, was significantly better in the deficient mice. Moreover, the deficient mice showed a restoration of neuromuscular system function below the lesion after electrical stimulation at the occipito-cervical area. In addition, axonal regrowth of both the corticospinal and raphespinal tracts was promoted in the deficient mice. In vitro assays using primary cerebellar granule neurons demonstrated that keratan sulfate proteoglycans were required for the proteoglycan-mediated inhibition of neurite outgrowth. These data collectively indicate that keratan sulfate expression is closely associated with functional disturbance after spinal cord injury. N-acetylglucosamine 6-O-sulfotransferase-1-deficient mice are a good model to investigate the roles of keratan sulfate in the CNS.

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Section: Discussionsupporting

confidence: 77%

N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

Ito¹,

Sakamoto²,

Imagama³

et al. 2010

J. Neurosci.

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“…It has been postulated that myelination may be facilitated in active lesions by inflammation and infiltrating (or microglial-derived) macrophages, which provide the tissue with growth factors (Diemel et al, 1998;Kotter et al, 2001) and/or cues, such as secreted semaphorins (Williams et al, 2007). Indeed, macrophages/microglia produce growth factors in vitro (Araujo and Cotman, 1992;Nakajima et al, 2007;Yin et al, 2009). However, considering the data from mouse models of demyelination, an elevated amount of FGF-2 within active lesions not only appears to favor the recruitment of FGFR1 ϩ OPCs but also to inhibit their differentiation toward myelinating oligodendrocytes (Armstrong et al, 2002(Armstrong et al, , 2006.…”

Section: Discussionmentioning

confidence: 99%

FGF-2 and Anosmin-1 Are Selectively Expressed in Different Types of Multiple Sclerosis Lesions

Clemente

Ortega²,

Arenzana³

et al. 2011

J. Neurosci.

114

148

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Multiple sclerosis is a demyelinating disease that affects ϳ2,000,000 people worldwide. In the advanced stages of the disease, endogenous oligodendrocyte precursors cannot colonize the lesions or differentiate into myelinating oligodendrocytes. During development, both FGF-2 and Anosmin-1 participate in oligodendrocyte precursor cell migration, acting via the FGF receptor 1 (FGFR1). Hence, we performed a histopathological and molecular analysis of these developmental modulators in postmortem tissue blocks from multiple sclerosis patients. Accordingly, we demonstrate that the distribution of FGF-2 and Anosmin-1 varies between the different types of multiple sclerosis lesions: FGF-2 is expressed only within active lesions and in the periplaque of chronic lesions, whereas Anosmin-1 is upregulated within chronic lesions and is totally absent in active lesions. We show that the endogenous oligodendrocyte precursor cells recruited toward chronic-active lesions express FGFR1, possibly in response to the FGF-2 produced by microglial cells in the periplaque. Also in human tissue, FGF-2 is upregulated in perivascular astrocytes in regions of the normal-appearing gray matter, where the integrity of the blood-brain barrier is compromised. In culture, FGF-2 and Anosmin-1 influence adult mouse oligodendrocyte precursor cell migration in the same manner as at embryonic stages, providing an explanation for the histopathological observations: FGF-2 attracts/ enhances its migration, which is hindered by Anosmin-1. We propose that FGF-2 and Anosmin-1 are markers for the histopathological type and the level of inflammation of multiple sclerosis lesions, and that they may serve as novel pharmacogenetic targets to design future therapies that favor effective remyelination and protect the blood-brain barrier.

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“…Usually, GAGs are covalently attached to a core protein, forming proteoglycans (PG). In the literature more than 100 GAG-binding proteins have been described such as aggrecan, apoE, fibronectin, fibroblast growth factor, laminin and type V collagen (Varki et al 1999), some of them being expressed by microglia (Shimojo et al 1991;Guillemin et al 1997;Saura et al 2003;Yin et al 2009). The SGAGbinding receptors are subdivided into the HS-, CS-and DSbinding proteins (Varki and Angata 2006).…”

Section: Sgag-binding Receptorsmentioning

confidence: 98%

Microglial carbohydrate-binding receptors for neural repair

2012

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Microglia are the resident immune cells of the central nervous system (CNS) and perform typical scavenging and innate immune functions. Their capacity to eliminate extracellular aggregates and apoptotic neural material without inflammation is crucial for brain tissue homeostasis and repair. To fulfill these tasks, microglia express a whole set of recognition receptors including toll-like (TLRs), carbohydrate-binding, Fc, complement and cytokine receptors. Receptors recognizing carbohydrate structures are strongly involved in microglial repair function. Carbohydrate-binding receptors can be divided into two major subgroups: the sulfated glycosaminoglycan (SGAG)-binding receptors and the lectins (Siglecs, galectins, selectins). SGAG-binding receptors recognize anionic structural motifs within extended SGAG chains. Siglecs bind to the sialic acid cap of the intact glycocalyx. Other lectin family members such as galectins recognize lactosamine units typically exposed after alteration of the glycocalyx. Dependent on the type of microglial carbohydrate-binding receptors that are stimulated, either a pro-inflammatory cytotoxic or an anti-inflammatory repair-promoting response is evoked. The carbohydrate-binding receptors are also crucial in regulating microglial function such as phagocytosis during neurodegenerative or neuroinflammatory processes. A balance between microglial carbohydrate-binding receptor signaling via an immunoreceptor tyrosine-based activation motif or an immunoreceptor tyrosine-based inhibitory motif is required to polarize microglial cells appropriately so that they create a microenvironment permissive for neural regenerative events.

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Transforming growth factor-β1 upregulates keratan sulfate and chondroitin sulfate biosynthesis in microglias after brain injury

Cited by 28 publications

References 53 publications

N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

N-Acetylglucosamine 6-O-Sulfotransferase-1-Deficient Mice Show Better Functional Recovery after Spinal Cord Injury

FGF-2 and Anosmin-1 Are Selectively Expressed in Different Types of Multiple Sclerosis Lesions

Microglial carbohydrate-binding receptors for neural repair

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