hgf-protein

HGF Protein (Hepatocyte Growth Factor)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">hgf-protein</th>
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<td class="label">Symbol</td>
<td><strong>HGF</strong></td>
</tr>
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<td class="label">Full Name</td>
<td>hgf-protein</td>
</tr>
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<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=HGF" target="_blank">Search UniProt</a></td>
</tr>
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<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/infection" style="color:#ef9a9a">Infection</a></td>
</tr>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">31 edges</a></td>
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Overview

Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine that acts as a ligand for the MET receptor tyrosine kinase[@mainardi2020]. HGF is a mesenchyme-derived growth factor that promotes cell proliferation, survival, migration, and morphogenesis through MET signaling[@honda2018]. In the nervous system, HGF acts as a neurotrophic factor supporting neuronal survival and regeneration[@kitabayashi2019].

Structure

HGF Protein (Hepatocyte Growth Factor)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">hgf-protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>HGF</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>hgf-protein</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=HGF" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/infection" style="color:#ef9a9a">Infection</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">31 edges</a></td>
</tr>
</table>

Overview

Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine that acts as a ligand for the MET receptor tyrosine kinase[@mainardi2020]. HGF is a mesenchyme-derived growth factor that promotes cell proliferation, survival, migration, and morphogenesis through MET signaling[@honda2018]. In the nervous system, HGF acts as a neurotrophic factor supporting neuronal survival and regeneration[@kitabayashi2019].

Structure

HGF is a heterodimeric protein:

• α-chain: 463 aa, contains N-terminal domain and kringle domains 1-4
• β-chain: 234 aa, serine protease-like domain
• Single chain precursor (pro-HGF): 697 aa
• Mature HGF: αβ heterodimer linked by disulfide bond
• Molecular weight: ~82 kDa (pro-HGF), ~69 kDa (mature)[@gherardi2006]

Normal Function

Growth Factor Activities

• Potent mitogen for epithelial and endothelial cells
• Stimulates cell scatter and branching morphogenesis
• Promotes angiogenesis
• Induces matrix metalloproteinase (MMP) expression

Receptor Signaling

• Binds MET receptor (c-Met)
• Activates multiple signaling pathways:
• RAS/MAPK (proliferation)
• PI3K/AKT (survival)
• PLC-γ (cytoskeletal changes)
• STAT3 (transcriptional activation)[@trusolino2010]

Tissue Repair

• Liver regeneration
• Wound healing
• Tissue morphogenesis

Role in Neurodegeneration

Alzheimer's Disease

• HGF/MET signaling is neuroprotective in AD models[@hgf2020]
• Reduces amyloid-β toxicity
• Promotes synaptic plasticity
• May improve cognitive function
• MET activation enhances [tau](/proteins/tau) clearance

Parkinson's Disease

• HGF protects dopaminergic [neurons](/entities/neurons)[@hgf2019]
• Promotes neurite outgrowth
• Reduces MPTP-induced toxicity
• May support graft integration in cell therapy

Amyotrophic Lateral Sclerosis

• Neuroprotective in ALS models
• Delays disease progression in SOD1 mice
• Supports motor neuron survival
• Promotes axonal regeneration[@hgf2021]

Peripheral Neuropathy

• Promotes nerve regeneration
• Supports Schwann cell function
• May aid diabetic neuropathy recovery

Therapeutic Targeting

Recombinant HGF

• HGF protein (KRK-013) in clinical trials
• Gene therapy approaches (AAV-HGF)

MET Agonists

• Small molecule MET activators
• HGF mimetics

• Potential for oncogenic effects (MET pathway in cancer)
• Must balance trophic effects with safety

Combination Therapy

• HGF with neurotrophic factors
• HGF with rehabilitation
• Cell therapy combinations[@sato2015]

Key Publications

[@mainardi2020]: [Nakamura et al., HGF discovery (1989)](https://pubmed.ncbi.nlm.nih.gov/2554941/)
[@honda2018]: [Bottaro et al., HGF as MET ligand (1991)](https://pubmed.ncbi.nlm.nih.gov/1843431/)
[@kitabayashi2019]: [Maina & Klein, HGF in nervous system (1999)](https://pubmed.ncbi.nlm.nih.gov/10516561/)
[@gherardi2006]: [Gherardi et al., HGF structure (2006)](https://pubmed.ncbi.nlm.nih.gov/16685150/)
[@trusolino2010]: [Trusolino et al., MET signaling (2010)](https://pubmed.ncbi.nlm.nih.gov/20531348/)
[@hgf2020]: [@7: Tsubata et al., HGF in AD (2020)]
[@hgf2019]: [@8: Kurosaki et al., HGF in PD (2019)]
[@hgf2021]: [@9: Koyama et al., HGF in ALS (2021)]
[@sato2015]: [Sato et al., HGF clinical applications (2015)](https://pubmed.ncbi.nlm.nih.gov/26399243/)

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References