HGF–Met Pathway in Regeneration and Drug Discovery

Biomedicines, 2014 · DOI: 10.3390/biomedicines2040275 · Published: October 31, 2014

Pharmacology Regenerative Medicine Genetics

Simple Explanation

Hepatocyte growth factor (HGF) is composed of an α-chain and a β-chain, and these chains contain four kringle domains and a serine protease-like structure, respectively. Activation of the HGF–Met pathway evokes dynamic biological responses that support morphogenesis (e.g., epithelial tubulogenesis), regeneration, and the survival of cells and tissues. Recombinant HGF protein and the expression vectors for HGF are biological drug candidates for the treatment of patients with diseases and injuries that are associated with impaired tissue function.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level: Review

Key Findings

1
The intravenous/systemic administration of recombinant HGF protein has been well tolerated in phase I/II clinical trials.
2
The phase-I and phase-I/II clinical trials of the intrathecal administration of HGF protein for the treatment of patients with amyotrophic lateral sclerosis and spinal cord injury, respectively, are ongoing.
3
Characterization of conditional Met knockout mice indicates that the HGF–Met pathway plays important roles in regeneration, protection, and homeostasis in various cells and tissues.

Research Summary

HGF was molecularly cloned as a growth factor for hepatocytes. The scatter factor, originally identified as a fibroblast-derived cell motility factor for epithelial cells, was shown to be an identical molecule to HGF. Promotion of cell survival (i.e., suppression of cell death) is a key biological action of HGF–Met pathway in development, regeneration, and therapeutics. In most cases in the relationship between growth factors and their receptors, a single growth factor activates multiple receptors that have structural similarities, while a single receptor has multiple ligands with structural similarities.

Practical Implications

Therapeutic Potential in Tissue Regeneration

Enhancing Met-mediated signaling could be therapeutic for diseases affecting tissue regeneration, protection, and homeostasis.

Treatment of Fibrotic Diseases

HGF treatment has shown effectiveness in reducing fibrosis and improving tissue function in disease models like liver cirrhosis and chronic kidney disease.

Application in Neurodegenerative Diseases

HGF exerts neuroprotective effects in animal models of cerebrovascular diseases, spinal cord injury, and neurodegenerative diseases.

Study Limitations

1
The precise molecular mechanisms underlying HGF-Met signaling in various contexts require further elucidation.
2
Clinical trials for HGF-based therapies are ongoing, and the long-term efficacy and safety need to be established.
3
The potential for off-target effects and unintended consequences of HGF modulation needs careful consideration.

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