Hepatocyte growth factor (HGF) attenuates gliosis and motoneuronal degeneration in the brainstem motor nuclei of a transgenic mouse model of ALS

Kadoyama, Keiichi; Funakoshi, Hiroshi; Ohya, Wakana; Nakamura, Toshikazu

doi:10.1016/j.neures.2007.08.017

Cited by 63 publications

(43 citation statements)

References 53 publications

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“…G93A/HGF-Tg mice demonstrated marked decreases in the numbers of microglia and reactive astrocytes, and an attenuation of the motoneuron loss. HGF overexpression prevented monocyte chemoattractant protein-1 induction, suppressed caspase activation, and increased expression of X chromosome-linked inhibition of apoptosis protein in the motoneurons of G93A mice (70). Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease in the brain stem and spinal cord, caused by the expansion of a polyglutamine tract in the androgen receptor (AR) protein, which diffusely accumulates as inclusions in nuclei.…”

Section: Hgf Transgenic Micementioning

confidence: 99%

Biological roles of hepatocyte growth factor‑Met signaling from genetically modified animals (Review)

Kato

2017

biom rep

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Abstract. Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and it stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its cognate receptor, Met. The HGF-Met signaling pathway contributes in a paracrine manner to the development of epithelial organs, exerts regenerative effects on the epithelium, and promotes the regression of fibrosis in numerous organs. Additionally, the HGF-Met signaling pathway is correlated with the biology of cancer types, neurons and immunity. In vivo analyses using genetic modification have markedly increased the profound understanding of the HGF-Met system in basic biology and its clinical applications. HGF and Met knockout (KO) mice are embryonically lethal. Therefore, amino acids in multifunctional docking sites of Met have been exchanged with specific binding motifs for downstream adaptor molecules in order to investigate the signaling potential of the HGF-Met signaling pathway. Conditional Met KO mice were generated using Cre-loxP methodology and characterization of these mice indicated that the HGF-Met signaling pathway is essential in regeneration, protection, and homeostasis in various tissue types and cells. Furthermore, the results of studies using HGF-overexpressing mice have indicated the therapeutic potential of HGF for various types of disease and injury. In the present review, the phenotypes of Met gene-modified mice are summarized. IntroductionHepatocyte growth factor (HGF). HGF was cloned as a growth factor for hepatocytes (1,2), is identical to scatter factor (SF) and was originally discovered as a fibroblast-derived cell motility factor for epithelial cells (3). HGF is located at 7q21, which spans >70 kb in length and consists of 18 exons. It encodes the inactive pre-pro-HGF, a single chain of 728 amino acids (83 kDa), which includes a signal sequence (1-31), a heavy α chain (69 kDa), and a light β chain (34 kDa). The exons encode the α chain, with four kringle structures (highly conserved triple disulfide loop structures), a short spacer region between the α and β chains, and the β chain (Fig. 1A) (4-6).HGF is produced and secreted by adjacent stromal and mesenchymal cells, it contributes to the development of epithelial organs in a paracrine fashion, exerts regenerative effects on epithelia in the liver, kidney, lung, and other tissues, and promotes the regression of fibrosis in numerous organs (7,8). Various growth factors, cytokines, and prostaglandins upregulate HGF gene expression, including basic fibroblast growth factor, oncostatin M, hypoxia-inducible factor 1α and nuclear factor-κB (NF-κB) (9). By contrast, transforming growth factor (TGF)-β1 was demonstrated to markedly downregulate HGF gene expression (10,11).HGF forms a family with HGF-like protein (HLP), a unique protein with a domain structure similar to that of HGF (12). Macrophage stimulating protein (MSP) was discovered as a serum protein that promoted mouse macrophage motility (13) Abbreviatio...

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Section: Hgf Transgenic Micementioning

confidence: 99%

Biological roles of hepatocyte growth factor‑Met signaling from genetically modified animals (Review)

Kato

2017

biom rep

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“…Inflammation: encompasses measures of immune-induced inflammation, including astrocyte (Nagai, Re et al 2007) and microglia (Hall, Andrus et al 1998) counts, gliosis and the release of nitric oxide and proinflammatory cytokines, which in combination with impaired growth factors/trophic support (Narai, Nagano et al 2005;Kadoyama, Funakoshi et al 2007), further inhibit the neural environment.…”

Section: Category Definitionsmentioning

confidence: 99%

Dynamic Meta-Analysis as a Therapeutic Prediction Tool for Amyotrophic Lateral Sclerosis

Mitchell¹,

Lee²

2012

Amyotrophic Lateral Sclerosis

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“…A number of neurotrophic factors have been proposed as being a promising avenue for gene therapy in light of their beneficial effects on animal models of ALS. Among the factors which have shown promise in facilitating neuroprotection in animal models are vascular endothelial growth factor (VEGF) [81][82][83][84], hepatocyte growth factor (HGF) [85], glial-derived neurotrophic factor (GDNF) [84,86,87], insulin-like growth factor 1 (IGF-1) [88][89][90] and granulocyte-colony stimulating factor (G-CSF) [91,92]. The delivery of these neurotrophic factors can be carried out by using different approaches, with emerging viral vector-based and cell-based therapies among some of the most promising techniques.…”

Section: Dysregulation Of Rna Processing Is Emerging As a Major Pathomentioning

confidence: 99%

Current developments in gene therapy for amyotrophic lateral sclerosis

Scarrott

Herranz-Martín

Alrafiah

et al. 2015

Expert Opinion on Biological Therapy

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Article highlights: Types of ALS and the recent genetic discoveries. No effective treatment for ALS is available. Gene therapy approaches to modulate mutant ALS genes by using siRNA or antisense oligonucleotide (ASO) therapy. AAV or LV-based vectors driving the expression of neurotrophic factors to support motor neuron survival. A summary of the previous and the ongoing gene therapy clinical trials for ALS.3

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Hepatocyte growth factor (HGF) attenuates gliosis and motoneuronal degeneration in the brainstem motor nuclei of a transgenic mouse model of ALS

Cited by 63 publications

References 53 publications

Biological roles of hepatocyte growth factor‑Met signaling from genetically modified animals (Review)

Biological roles of hepatocyte growth factor‑Met signaling from genetically modified animals (Review)

Dynamic Meta-Analysis as a Therapeutic Prediction Tool for Amyotrophic Lateral Sclerosis

Current developments in gene therapy for amyotrophic lateral sclerosis

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