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Hepatocyte growth factor activator (HGFA) is a serine protease initially identified as a potent activator of hepatocyte growth factor⁄scatter factor. Hepatocyte growth factor⁄scatter factor is known to be critically involved in tissue morphogenesis, regeneration, and tumor progression, via its recep-tor, MET. In vivo, HGFA also activates macrophage-stimulating protein, which has roles in macrophage recruitment and inflammatory processes, cellular survival and wound healing through its receptor, RON | MINIREVIEW Hepatocyte growth factor activator HGFA pathophysiological functions in vivo Hiroaki Kataoka and Makiko Kawaguchi Section of Oncopathology and Regenerative Biology Faculty of Medicine University of Miyazaki Japan Keywords hepatocyte growth factor hepatocyte growth factor activator HGF activator macrophage-stimulating protein tissue injury Correspondence H. Kataoka Section of Oncopathology and Regenerative Biology Faculty of Medicine University of Miyazaki 5200 Kihara Kiyotake Miyazaki 889-1692 Japan Fax 81 985 856003 Tel 81 985 852809 E-mail mejina@med.miyazaki-u.ac.jp Received 17 November 2009 revised 21 January 2010 accepted 26 February 2010 doi 10.1111 j.1742-4658.2010.07640.x Hepatocyte growth factor activator HGFA is a serine protease initially identified as a potent activator of hepatocyte growth factor scatter factor. Hepatocyte growth factor scatter factor is known to be critically involved in tissue morphogenesis regeneration and tumor progression via its receptor MET. In vivo HGFA also activates macrophage-stimulating protein which has roles in macrophage recruitment and inflammatory processes cellular survival and wound healing through its receptor RON. Therefore the pericellular activity of HGFA might be an important factor regulating the activities of these multifunctional cytokines in vivo. HGFA is secreted mainly by the liver circulates in the plasma as a zymogen pro-HGFA and is activated in response to tissue injury including tumor growth. In addition local production of pro-HGFA by epithelial stromal or tumor cells has been reported. Although the generation of HGFA-knockout mice revealed that the role played by HGFA in normal development and physiological settings can be compensated for by other protease systems HGFA has important roles in regeneration and initial macrophage recruitment in injured tissue in vivo. Insufficient activity of HGFA results in impaired regeneration of severely damaged mucosal epithelium and may contribute to .
