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

• Autor: Fukushima, Tsuyoshi ; Uchiyama, Shuichiro ; Tanaka, Hiroyuki ; Kataoka, Hiroaki
• Assuntos: Alarmins - metabolism ; Animals ; c-Met protein ; Cell activation ; Coagulation ; Coagulation factor XII ; Coagulation factors ; Endopeptidases ; Growth factors ; Hepatectomy ; Hepatocyte growth factor ; Hepatocyte Growth Factor - pharmacology ; hepatocyte growth factor activator ; HGF ; Humans ; Inflammation ; Inflammation - pathology ; Kallikrein ; Kinases ; Liver ; Macrophages ; Mesenchyme ; MET ; Nervous system ; Paracrine signalling ; Peptidase ; Peptidases ; Physiology ; Plasma ; Proenzymes ; protease ; Protein Precursors - pharmacology ; Protein-tyrosine kinase receptors ; Proteinase ; Proteins ; Proteolysis ; Regeneration ; Repair ; Review ; Ron protein ; Serine Endopeptidases - chemistry ; Serine Endopeptidases - pharmacology ; Signaling ; Stem cells ; Thrombin ; Tissue engineering ; tissue injury ; tissue repair ; Tyrosine ; Wound Healing - drug effects ; Wounds and Injuries - pathology
• É parte de: International journal of molecular sciences, 2018-11, Vol.19 (11), p.3435
• Notas: ObjectType-Article-2
  SourceType-Scholarly Journals-1
  ObjectType-Feature-3
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  ObjectType-Review-1
  
• Descrição: 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.
  
• Editor: Switzerland: MDPI AG
  
• Idioma: Inglês