GM-CSF regulates the ERK1/2 pathways and protects injured retinal ganglion cells from induced death

Schallenberg, Maurice; Charalambous, Petar; Thanos, Solon

doi:10.1016/j.exer.2009.06.008

Cited by 34 publications

(40 citation statements)

References 42 publications

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“…Its receptor is expressed within the nervous system including the facial nucleus [53], whole retina [51], and cortex [44]. There are recent lines of evidence that GM-CSF has neuroprotective activities in retinal ganglion cells (RGCs) [51]. GM-CSF appears to be locally produced and acts either direct on RGCs or via regulating the function of microglial cells, which are of hematopoietic origin and resemble intraneural resident dendritic cells [54,55].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…GM-CSF is also expressed within the whole retina and appears to be involved in modulating neural and glial cell functions [49,51,52]. Its receptor is expressed within the nervous system including the facial nucleus [53], whole retina [51], and cortex [44].…”

Section: Introductionmentioning

confidence: 99%

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GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins

Schallenberg

Charalambous

Thanos

2012

Graefes Arch Clin Exp Ophthalmol

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins

Schallenberg

Charalambous

Thanos

2012

Graefes Arch Clin Exp Ophthalmol

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“…GM-CSF promotes the mobilization of EPCs, resulting in improved vascularization in mice [9] and increased myocardial collateral blood flow in patients with coronary artery disease [10], and it accelerates the proliferation of EPCs derived from murine bone marrow mononuclear cells [11]. GM-CSF signaling is mediated by several kinase cascades including MAPK, Janus kinase (JAK)/signal transducers and activators of transcription 5 (Stat5) and phosphatidylinositide 3 (PI3) Kinase [7,12,13,14,15]. …”

Section: Introductionmentioning

confidence: 99%

GM-CSF Induces Cyclin D1 Expression and Proliferation of Endothelial Progenitor Cells via PI3K and MAPK Signaling

Qiu

Xie

Zhang³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Endothelial progenitor cells (EPCs), which can be isolated from the bone marrow or the peripheral blood, have generated interest because of their capacity to migrate to sites of vascularization and endothelialization and differentiate into endothelial cells in a process termed neovasculogenesis. EPCs are therefore possible regenerative tools for the treatment of vascular diseases and potential targets for the inhibition of angiogenesis during tumor development. Here, we investigated the mechanisms underlying the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the acceleration of EPC proliferation and colony formation. Methods: EPCs were isolated, identified and cultured in the presence of GM-CSF. The effect of GM-CSF on endothelial cell colony formation and proliferation was examine by colony formation assay and MTT assay, separately. Cell cycle was analyzed by flow cytometry. The expression of cyclin D1 and cyclin E were detected by western bloting. JAK/Stat, PI3K/Akt and MAPK signaling were analyzed. Results: GM-CSF accelerated the G1/S phase transition in EPCs by upregulating the expression of cyclins D1 and E. The GM-CSF induced increase in the levels of cyclin D1 and the subsequent phosphorylation of the retinoblastoma (Rb) protein activated E2F-1, resulting in the upregulation of the transcription of cyclin E. Furthermore, the induction of cyclin D1 expression and cell cycle progression by GM-CSF was mediated by the PI3K/Akt, JNK and ERK signaling pathways through the phosphorylation of GSK3β or the activation of AP-1 transcription factors. Conclusion: Our findings shed light on the mechanisms underlying the effect of GM-CSF on the modulation of cell cycle progression in EPCs, which is important considering their role in vascular repair and their therapeutic potential in several diseases.

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“…GM-CSF was previously reported as having a neuroprotective effect after staurosporin-induced apoptosis in retinal ganglion cells and in the vitreous bodies of Sprague-Dawley rats. 42 It has also been described to control glial scar composition and influence the survival and function of neighboring neurons. 43 Thus, it is possible that hypoxia-induced GM-CSF in EpoSV-GM-CSF NSCs protects the host organs by means of autocrine and paracrine effects.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury

Kim

et al. 2011

Gene Ther

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the differentiation and function of hematopoietic cells. GM-CSF has been implicated in nervous system function. The goal of the present study was to understand the effects of hypoxia-induced GM-CSF on neural stem cells (NSCs) in a model of spinal cord injury (SCI). GM-CSF-overexpressing NSCs were engineered utilizing a hypoxia-inducible gene expression plasmid, including an Epo enhancer ahead of an SV promoter (EpoSV-GM-CSF). Cells were then subjected to hypoxia (pO 2 , 1%) or a hypoxia-mimicking reagent (CoCl 2 ) in vitro. The progression of time of GM-CSF expression was tracked in EpoSV-GM-CSF-transfected NSCs. Overexpression of GM-CSF in undifferentiated and differentiated NSCs created resistance to H 2 O 2 -induced apoptosis in hypoxia. NSCs transfected with EpoSV-GM-CSF or SV-GM-CSF were transplanted into rats after SCI to assess the effect of GM-CSF on NSC survival and restoration of function. Moreover, a significantly higher amount of surviving NSCs and neuronal differentiation was observed in the EpoSV-GM-CSF-treated group. Significant improvement in locomotor function was also found in this group. Thus, GM-CSF overexpression by the Epo enhancer in hypoxia was beneficial to transplanted NSC survival and to behavioral improvement, pointing toward a possible role for GM-CSF in the treatment of SCI.

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GM-CSF regulates the ERK1/2 pathways and protects injured retinal ganglion cells from induced death

Cited by 34 publications

References 42 publications

GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins

GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins

GM-CSF Induces Cyclin D1 Expression and Proliferation of Endothelial Progenitor Cells via PI3K and MAPK Signaling

Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury

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