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Biomedicines 2014, 2(4), 275-300; doi:10.3390/biomedicines2040275

HGF–Met Pathway in Regeneration and Drug Discovery

1
Division of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Japan
2
Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa 078-8510, Japan
*
Author to whom correspondence should be addressed.
Received: 25 August 2014 / Revised: 15 September 2014 / Accepted: 13 October 2014 / Published: 31 October 2014
(This article belongs to the Special Issue New aspects of the Hepatocyte Growth Factor/c-Met System)
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Abstract

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. Characterizations of conditional Met knockout mice have indicated that the HGF–Met pathway plays important roles in regeneration, protection, and homeostasis in various cells and tissues, which includes hepatocytes, renal tubular cells, and neurons. Preclinical studies designed to address the therapeutic significance of HGF have been performed on injury/disease models, including acute tissue injury, chronic fibrosis, and cardiovascular and neurodegenerative diseases. The promotion of cell growth, survival, migration, and morphogenesis that is associated with extracellular matrix proteolysis are the biological activities that underlie the therapeutic actions of HGF. 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. The intravenous/systemic administration of recombinant HGF protein has been well tolerated in phase I/II clinical trials. 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. View Full-Text
Keywords: amyotrophic lateral sclerosis; clinical trial; HGF; Met; spinal cord injury amyotrophic lateral sclerosis; clinical trial; HGF; Met; spinal cord injury
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Matsumoto, K.; Funakoshi, H.; Takahashi, H.; Sakai, K. HGF–Met Pathway in Regeneration and Drug Discovery. Biomedicines 2014, 2, 275-300.

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