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Hepatocyte Growth Factor Activator: A Proteinase Linking Tissue Injury with Repair

1
Section of Oncopathology and Regenerative Biology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake 889-1692, Miyazaki, Japan
2
Department of Surgery, Miyakonojyo Medical Association Hospital, 1364-1 Tarobocho, Miyakonojyo 885-0002, Miyazaki, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3435; https://doi.org/10.3390/ijms19113435
Received: 27 September 2018 / Revised: 22 October 2018 / Accepted: 30 October 2018 / Published: 1 November 2018
(This article belongs to the Special Issue Hepatocyte Growth Factor (HGF))
Hepatocyte growth factor (HGF) promotes pleiotropic signaling through its specific receptor tyrosine kinase, MET. As such, it has important roles in the regeneration of injured tissues. Since HGF is produced mainly by mesenchymal cells and MET is expressed in most epithelial, endothelial and somatic stem cells, HGF functions as a typical paracrine growth factor. HGF is secreted as an inactive precursor (proHGF) and requires proteolytic activation to initiate HGF-induced MET signaling. HGF activator (HGFAC) is a serum activator of proHGF and produces robust HGF activities in injured tissues. HGFAC is a coagulation factor XII-like serine endopeptidase that circulates in the plasma as a zymogen (proHGFAC). Thrombin, kallikrein-related peptidase (KLK)-4 or KLK-5 efficiently activates proHGFAC. The activated HGFAC cleaves proHGF at Arg494-Val495, resulting in the formation of the active disulfide-linked heterodimer HGF. Macrophage stimulating protein, a ligand of RON, is also activated by HGFAC in vivo. Although HGFAC functions primarily at the site of damaged tissue, a recent report has suggested that activated HGFAC relays a signal to stem cells in non-injured tissues via proHGF activation in the stem cell niche. This review focuses on current knowledge regarding HGFAC-mediated proHGF activation and its roles in tissue regeneration and repair. View Full-Text
Keywords: hepatocyte growth factor activator; HGF; MET; protease; tissue injury; tissue repair hepatocyte growth factor activator; HGF; MET; protease; tissue injury; tissue repair
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Fukushima, T.; Uchiyama, S.; Tanaka, H.; Kataoka, H. Hepatocyte Growth Factor Activator: A Proteinase Linking Tissue Injury with Repair. Int. J. Mol. Sci. 2018, 19, 3435.

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