HGF promotes survival and growth of maturing sympathetic neurons by PI-3 kinase- and MAP kinase-dependent mechanisms

Thompson, Jane L.; Dolcet, Xavier; Hilton, Mark; Tolcos, Mary; Davies, Alun M.

doi:10.1016/j.mcn.2004.07.007

Cited by 59 publications

(53 citation statements)

References 60 publications

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“…In agreement with this, we found that Rit activates ERK1/2 in neurons and pharmacological inhibition of MEK1 blocks both the axon-promoting and dendrite-inhibiting activity of caRit. These data are consistent with reports that MEK/ERK signaling enhances axonal growth in sympathetic (Atwal et al, 2000;Thompson et al, 2004) and hippocampal (Gerecke et al, 2004) neurons and with our previous observations that BMP7-induced dendritic growth in sympathetic neurons is potentiated by inhibition of MEK/ERK activation (Kim et al, 2004). However, our findings contrast with reports that MEK/ERK signaling mediates activitydependent increases in dendritic growth in both hippocampal (Wayman et al, 2006) and sympathetic neurons (Vaillant et al, 2002), suggesting that MEK/ ERK activation alone is not sufficient to fully explain Rit effects on axonal and dendritic growth.…”

Section: Discussionsupporting

confidence: 93%

The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

Lein¹,

Guo²,

Shi³

et al. 2007

J. Neurosci.

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The Rit GTPase is widely expressed in developing and adult nervous systems, and our previous data with pheochromocytoma cells implicate Rit signaling in NGF-induced neurite outgrowth. In this study, we investigated a role for Rit in neuronal morphogenesis. Expression of a dominant-negative (dn) Rit mutant in hippocampal neurons inhibited axonal growth but potentiated dendritic growth. Conversely, a constitutively active (ca) Rit mutant promoted axonal growth but inhibited dendritic growth. Dendritogenesis is regulated differently in sympathetic neurons versus hippocampal neurons in that sympathetic neurons require NGF and bone morphogenetic proteins (BMPs) to trigger dendritic growth. Despite these differences, dnRit potentiated and caRit blocked BMP7-induced dendritic growth in sympathetic neurons. Biochemical studies indicated that BMP7 treatments that caused dendritic growth also decreased Rit GTP loading. Additional studies demonstrate that caRit increased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and pharmacological inhibition of MEK1 (mitogen-activated protein kinase/ERK 1) blocked the axon-promoting and dendrite-inhibiting effects of caRit. These observations suggest that Rit is a convergence point for multiple signaling pathways and it functions to promote axonal growth but inhibit dendritic growth via activation of ERK1/2. Modulation of the activational status of Rit may therefore represent a generalized mechanism across divergent neuronal cell types for regulating axonal versus dendritic growth modes.

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Section: Discussionsupporting

confidence: 93%

The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

Lein¹,

Guo²,

Shi³

et al. 2007

J. Neurosci.

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“…However, LY294002 reduced Complexmediated enhancement of neurite outgrowth, demonstrating a dependence of Complex on the PI3K pathway. Complementing our finding, inhibition of the PI3K/Akt pathway restricts neurite outgrowth mediated by other growth factors and cytokines, including hepatocyte growth factor, brain-derived neurotrophic factor, NGF, NRG-1␤, and BMP-7 (67)(68)(69)(70)(71).…”

Section: Discussionsupporting

confidence: 78%

Co-administration of Ciliary Neurotrophic Factor with Its Soluble Receptor Protects against Neuronal Death and Enhances Neurite Outgrowth

Ozog¹,

Modha

Church

et al. 2008

Journal of Biological Chemistry

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Attempts to promote neuronal survival and repair with ciliary neurotrophic factor (CNTF) have met with limited success. The variability of results obtained with CNTF may, in part, reflect the fact that some of the biological actions of the cytokine are mediated by a complex formed between CNTF and its specific receptor, CNTFR␣, which exists in both membrane-bound and soluble forms. In this study, we compared the actions of CNTF alone and CNTF complexed with soluble CNTFR␣ (hereafter termed "Complex") on neuronal survival and growth. Although CNTF alone produced limited effects, Complex protected against glutamate-mediated excitotoxicity via gap junction-dependent and -independent mechanisms. Further examination revealed that only Complex promoted neurite outgrowth. Differential gene expression analysis revealed that, compared with CNTF alone, Complex differentially regulates several neuroprotective and neurotrophic genes. Collectively, these findings indicate that CNTF exerts more robust effects on neuronal survival and growth when applied in combination with its soluble receptor.

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“…30 HGF is reported to phosphorylate Akt, and blockade of Akt activation with the phosphatidylinositol-3 kinase (PI3-K) inhibitor, LY294002, inhibited the survival response in maturing sympathetic neurons by HGF. 31 HGF also prevented hippocampal cell death in rats with transient forebrain ischemia 32 through phosphorylation of extracellular signal-regulated kinase. Since PI3-K/Akt inhibits reactive oxygen species production through rac1, 32,33 HGF might reduce oxidative stress through the PI3-K/Akt pathway.…”

Section: Discussionmentioning

confidence: 89%

Alleviation of Aβ-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model

et al. 2008

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A new therapeutic approach to treat Alzheimer's disease (AD) is needed, and the use of growth factors is considered to be a candidate. Hepatocyte growth factor (HGF) is a unique multifunctional growth factor, which has the potential effect to exert neurotrophic action and induce angiogenesis. In this study, we examined the effects of overexpression of human HGF plasmid DNA using ultrasound-mediated gene transfer into the brain in an Ab-infused cognitive dysfunction mouse model. We demonstrated that HGF gene transfer significantly alleviated Ab-induced cognitive impairment in mice in behavioral tests. These beneficial effects of HGF might be due to (1) significant recovery of the vessel density in the dentate gyrus of the hippocampus, (2) upregulation of BDNF, (3) a significant decrease in oxidative stress and (4) synaptic enhancement. A pharmacological approach including gene therapy to increase the HGF level in combination with anti-Ab therapy might be a new therapeutic option for the treatment of AD.

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HGF promotes survival and growth of maturing sympathetic neurons by PI-3 kinase- and MAP kinase-dependent mechanisms

Cited by 59 publications

References 60 publications

The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

The Novel GTPase Rit Differentially Regulates Axonal and Dendritic Growth

Co-administration of Ciliary Neurotrophic Factor with Its Soluble Receptor Protects against Neuronal Death and Enhances Neurite Outgrowth

Alleviation of Aβ-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model

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