Basic fibroblast growth factor: a potential inhibitor of glutamine synthetase expression in injured neural tissue

Kruchkova, Yelena; Ben-Dror, Iris; Herschkovitz, Avia; David, Michel; Yayon, Avner; Vardimon, Lily

doi:10.1046/j.1471-4159.2001.00390.x

Cited by 45 publications

(34 citation statements)

References 50 publications

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“…GS expression is a symptom of glial maturation and can be induced in immature Müller glia by exogenous glucocorticoids (Moscona and Linser, 1983); this is probably a direct effect as GCR may be expressed by immature glia or latestage retinal progenitors . By comparison, FGF2 inhibits the expression of GS in the developing retina (Kruchkova et al, 2001), consistent with the notion that FGF signaling promotes the de-differentiation of Müller glia and maintains neural progenitors (reviewed by Fischer and Bongini, 2010;Gallina et al, 2014). In the retinas of different vertebrate species, proliferating Müller glia-derived retinal progenitor cells (MGPCs) are generated in response to damage or activation of distinct cell-signaling pathways (reviewed by Fischer and Bongini, 2010;Gallina et al, 2014).…”

Section: Introductionsupporting

confidence: 57%

Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

2014

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Identification of the signaling pathways that influence the reprogramming of Müller glia into neurogenic retinal progenitors is key to harnessing the potential of these cells to regenerate the retina. Glucocorticoid receptor (GCR) signaling is commonly associated with anti-inflammatory responses and GCR agonists are widely used to treat inflammatory diseases of the eye, even though the cellular targets and mechanisms of action in the retina are not well understood. We find that signaling through GCR has a significant impact upon the ability of Müller glia to become proliferating Müller glia-derived progenitor cells (MGPCs). The primary amino acid sequence and pattern of GCR expression in the retina is highly conserved across vertebrate species, including chickens, mice, guinea pigs, dogs and humans. In all of these species we find GCR expressed by the Müller glia. In the chick retina, we find that GCR is expressed by progenitors in the circumferential marginal zone (CMZ) and is upregulated by Müller glia in acutely damaged retinas. Activation of GCR signaling inhibits the formation of MGPCs and antagonizes FGF2/MAPK signaling in the Müller glia. By contrast, we find that inhibition of GCR signaling stimulates the formation of proliferating MGPCs in damaged retinas, and enhances the neuronal differentiation while diminishing glial differentiation. Given the conserved expression pattern of GCR in different vertebrate retinas, we propose that the functions and mechanisms of GCR signaling are highly conserved and are mediated through the Müller glia. We conclude that GCR signaling directly inhibits the formation of MGPCs, at least in part, by interfering with FGF2/MAPK signaling.

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Section: Introductionsupporting

confidence: 57%

Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

2014

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“…For example, ceftriaxone, which upregulated GLT-1 expression, blocked elevated GFAP expression (24,25). By contrast, downregulation of GLT-1 and GS occurred in activated astrocytes characteristic of increased GFAP expression (26). The present results further verified the antagonism between the expression of GLT-1 and GS and glial cell proliferation.…”

Section: Discussionsupporting

confidence: 86%

Buyang Huanwu decoction increases the expression of glutamate transporter-1 and glutamate synthetase in association with PACAP-38 following focal ischemia

Ding

Liu

et al. 2015

Biomedical Reports

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Abstract. The neuroprotective role of Buyang Huanwu decoction (BYHWD) in focal ischemia is associated with decreasing glutamate concentration. However, the mechanisms are not fully understood. The present study aimed to explore whether glutamate transporter-1 (GLT-1) and glutamine synthetase (GS) participated in the decreased level of glutamate and whether pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) was involved in this process. BYHWD was found to significantly upregulate the expression of GLT-1 and GS in the hippocampal CA1 area compared to the ischemia group, with the difference on day 3 being most significant. BYHWD increased the level of PACAP-38, and PACAP-(6-38) (PACAP receptor antagonist) significantly attenuated the effect of BYHWD on GLT-1 and GS, suggesting that PACAP-38 was involved in the upregulation of GLT-1 and GS induced by BYHWD. In addition, as GLT-1 and GS are mainly located in astrocytes, the changes of astrocytes were detected by glial fibrillary acidic protein (GFAP; an astrocytic marker) immunostaining. The results showed that BYHWD inhibited the expression of GFAP compared with the ischemia group, however, co-administration with PACAP-(6-38), which inhibited the effect of BYHWD on GLT-1 and GS in astrocytes, attenuated this effect, indicating that astrocytes participated in the protective role of BYHWD following focal ischemia. These results provided the evidence for the first time that not only neurons but also astrocytes contribute to the protective role of BYHWD, which opposes previous studies and may be a starting point for traditional medicine.

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“…Our combined in situ and immunofluorescence stainings suggest that cells expressing high levels of LIF have reduced GS levels. Whether this is an artificial observation due to the staining procedure needs to be analyzed but it is interesting that GS might be down regulated in pathological situations possibly through the action of FGF2 (Kruchkova et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Leukemia Inhibitory Factor Extends the Lifespan of Injured PhotoreceptorsIn Vivo

Joly¹,

Lange²,

Thiersch³

et al. 2008

J. Neurosci.

120

168

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Survival and death of photoreceptors in degenerative diseases of the retina is controlled by a multitude of genes and endogenous factors. Some genes may be involved in the degenerative process itself whereas others may be part of an endogenous defense system. We show in two models of retinal degeneration that photoreceptor death strongly induces expression of leukemia inhibitory factor (LIF) in a subset of Muller glia cells in the inner nuclear layer of the retina. LIF expression is essential to induce an extensive intraretinal signaling system which includes Muller cells and photoreceptors and is characterized by an upregulation of Edn2, STAT3, FGF2 and GFAP. In the absence of LIF, Muller cells remain quiescent, the signaling system is not activated and retinal degeneration is strongly accelerated. Intravitreal application of recombinant LIF induces the full molecular pathway including the activation of Muller cells in wild-type and Lif -/-mice. Interruption of the signaling cascade by an Edn2 receptor antagonist increases whereas activation of the receptor decreases photoreceptor cell death. Thus, LIF is essential and sufficient to activate an extensive molecular defense response to photoreceptor injury. Our data establish LIF as a Muller cell derived neuronal survival factor which controls an intrinsic protective mechanism that includes Edn2 signaling to support photoreceptor cell survival and to preserve vision in the injured retina.

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Basic fibroblast growth factor: a potential inhibitor of glutamine synthetase expression in injured neural tissue

Cited by 45 publications

References 50 publications

Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

Buyang Huanwu decoction increases the expression of glutamate transporter-1 and glutamate synthetase in association with PACAP-38 following focal ischemia

Leukemia Inhibitory Factor Extends the Lifespan of Injured PhotoreceptorsIn Vivo

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