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Hepatocyte growth factor and its signalling, new horizons in medicine and therapies.

Jiang, Wen Guo and Matsumoto, Kei 2011. Hepatocyte growth factor and its signalling, new horizons in medicine and therapies. Current Signal Transduction Therapy 6 (2) , pp. 141-142.

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Hepatocyte growth factor (HGF, otherwise known as scatter factor, SF) was discovered more than two decades ago. During this period, the HGF receptor, cMET has been identified, the signalling pathways downstream of HGF/cMET have been reported. Two decade on, hepatocyte growth factor, its receptor and cellular signalling have been increasingly recognised as important in a number of physiological processes and pathological conditions. Ways to utilise HGF, or to target HGF, the HGF receptor and HGF signalling pathways have been attempted, some being used in early stage of clinical studies. The current issue explores some of the leading work in this pivotal area. We are indebted to Dr. Toshikazu Nakamura, Professor Emeritus of Osaka University, who first cloned HGF in 1989 [1] and has provided his insightful and excellent views of the discovery of HGF, the evolution of studies on HGF from scientific investigation to preclinical and clinical studies as well as the therapeutic implications [2]. Perhaps it is the initial discovery of the molecule from three different directions, namely as a hepatopietic protein [3], a mitogenic protein to hepatocyte [4], and a protein causing scattering of epithelial cells [5], that has lead to the areas of subsequent investigations into the biological and clinical impact of the molecule. It is now known that the molecule is widely involved in the pathophysiology of the liver, in the morphogenesis regulation of varying tissues and cells, and a powerful regulator of angiogenesis and lymphangiogenesis. A number of clinical and therapeutic implication have been developed along these main function of the cells as indicated by Professor Nakamura [2]. The clinical and therapeutic implication of HGF and its signalling is clearly discussed by Oka et al., [6]. Being one of the most powerful protein mitogen for hepatocytes and for liver regeneration, the action of HGF on liver is well beyond on hepatocytes. It influences the fibrosis, lipidosis, inflammation and necrosis via its action on the non-parenchymal cells such as myofibroblasts. Such being the case, HGF has now been widely tested in liver conditions including various types of hepatitis and liver cirrhosis. Two examples of HGF being a useful therapeutic option in the area of regeneration are lung [7] and wound healing [8]. Mizuno et al., [7] has discussed the pivotal role of HGF in the physiology and pathology of lung conditions and documented the potential therapeutic implications of HGF in both acute and chronic lung diseases. Both HGF and its regulators, including HGF-activater (HGF-A) and HGF-A inhibitors (HAIs) are aberrant in wound healing and are indicators of abnormal wound healing [8]. Funakoshi and Nakamura have covered an area that have less well recognised in the past, the role of HGF in the neuronal development and injuries [9]. Recent evidience has shown that HGF is a novel neurotrophic factor for a variety of neurons both in vitro and in vivo. It is also fascinating to observe that apart from physically acting on the neurons, HGF has also been indicated in the behaviour regulation of the nervous system and has been shown to be linked to autism and schizophrenia, thus pointing HGF being an important target and therapeutic means in both neuronal and behaviour condition, a new horizon for HGF. The other important aspect of HGF as morphogenic regulators are discussed in relation with angiogenesis [10] and lymphangiogenesis [11], both are important biological process in cardiovascular conditions and cancer spread. HGF and its receptor have been widely studied in the context of cancer and cancer metastasis, over the last two decades. A great deal has learned with regard to the expression profile of the cytokine complex in virtually all the tumour types in humans. Apart from a direction action on cancer cells, HGF also acts on other cells and mechanisms that facility the progression of cancer, including endothelial cells, stromal and immune cells.

Item Type: Article
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Additional Information: Editorial (Hot Topic)
Publisher: Bentham Science Publishers
ISSN: 1574-3624
Last Modified: 04 Jun 2017 03:21

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