HGF–Met Pathway in Regeneration and Drug Discovery

Biomedicines

Kunio Matsumoto²  Hiroshi Funakoshi¹  Hisaaki Takahashi¹  Katsuya Sakai² 

[1] Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa 078-8510, Japan; E-Mails:;Division of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Japan; E-Mail:

关键词: amyotrophic lateral sclerosis;    clinical trial;    HGF;    Met;    spinal cord injury;   

DOI  :  10.3390/biomedicines2040275

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.