scholarly journals Proteolytic activation of hepatocyte growth factor in response to tissue injury.

1994 ◽  
Vol 269 (12) ◽  
pp. 8966-8970
Author(s):  
K. Miyazawa ◽  
T. Shimomura ◽  
D. Naka ◽  
N. Kitamura
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tissue Injury ◽  
Proteolytic Activation ◽  
Hepatocyte Growth

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

2018 ◽  
Vol 19 (11) ◽  
pp. 3435 ◽  
Author(s):  
Tsuyoshi Fukushima ◽  
Shuichiro Uchiyama ◽  
Hiroyuki Tanaka ◽  
Hiroaki Kataoka
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tissue Injury ◽  
Current Knowledge ◽  
Coagulation Factor ◽  
Factor Xii ◽  
Proteolytic Activation ◽  
Hepatocyte Growth

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.

scholarly journals Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation

2021 ◽  
Author(s):  
Hsuan-Shun Huang ◽  
Pao-Chu Chen ◽  
Sung-Chao Chu ◽  
Ming-Hsun Lee ◽  
Chi-Ya Huang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Malignant Transformation ◽  
Blood Circulation ◽  
Tissue Injury ◽  
Serous Carcinoma ◽  
Transient Event ◽  
Transformation Activity ◽  
Hepatocyte Growth

The fallopian tube fimbrial epithelium (FTE), which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma (HGSC). Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of FTE. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor-thrombin-HGFA-HGF cleavage cascade confers a sustained transformation activity to FTE, HGSC. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.

The constitutive high-affinity Met-binding site in the kringle domain is dispensable for the signalling activity of hepatocyte growth factor

2020 ◽  
Vol 167 (6) ◽  
pp. 577-586
Author(s):  
Masataka Umitsu ◽  
Katsuya Sakai ◽  
Keiko Tamura-Kawakami ◽  
Kunio Matsumoto ◽  
Junichi Takagi
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Size Exclusion ◽  
Receptor Interaction ◽  
Tyrosine Kinase Receptor ◽  
Single Chain ◽  
Kringle Domain ◽  
Proteolytic Activation ◽  
High Affinity ◽  
Hepatocyte Growth

Abstract Activation of a tyrosine kinase receptor Met by hepatocyte growth factor (HGF) requires binding of proteolytically activated, two-chain (tc) HGF, but the biochemical detail of this ligand–receptor interaction specificity remains elusive because biologically inactive single chain (sc) HGF can also bind to Met with high affinity. We found that this proteolysis-independent Met binding can be eliminated by mutagenesis introduced in the kringle domain without losing the ability to bind and activate cellular Met receptor after proteolytic activation, arguing against this site’s involvement in the physiological signalling. This non-signal producing Met–HGF interaction can also be eliminated by addition of a heparin mimetic sucrose octasulphate (SOS). By including SOS in the running buffer, we succeeded in detecting cleavage-dependent tcHGF–Met complex formation by size exclusion chromatography.

scholarly journals Hepatocyte growth factor stimulates neutrophil degranulation but not respiratory burst

1993 ◽  
Vol 2 (2) ◽  
pp. 129-133 ◽  
Author(s):  
I. C. Kowanko ◽  
A. Ferrante ◽  
T. Nakamura
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Respiratory Burst ◽  
Tissue Injury ◽  
Cell Types ◽  
Neutrophil Function ◽  
Enzyme Release ◽  
Neutrophil Degranulation ◽  
Different Cell Types ◽  
Hepatocyte Growth

Neutrophil function is regulated in part by cytokines with growth factor activities for different cell types. Hepatocyte growth factor (HGF) is a cytokine produced during injury to the liver and other organs. Neutrophils are numerous in such tissue injury sites and may be influenced by HGF. In the present study the effect of HGF on neutrophils was investigated. The data show that HGF at 1–10 ng/ml increased lysosomal enzyme release from both specific and azurophilic granules of cytochalasin-B treated neutrophils. The release of specific granule contents in response to N-formyl-methionyl-leucylphenylalanine was also increased by HGF. In contrast there were no significant effects of HGF on neutrophil respiratory burst, adherence or locomotion. It is concluded that HGF modulates neutrophil granule exocytosis.

scholarly journals Unusual Proteolytic Activation of Pro-hepatocyte Growth Factor by Plasma Kallikrein and Coagulation Factor XIa

2002 ◽  
Vol 277 (49) ◽  
pp. 47804-47809 ◽  
Author(s):  
Mark Peek ◽  
Paul Moran ◽  
Nerissa Mendoza ◽  
Dineli Wickramasinghe ◽  
Daniel Kirchhofer
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Coagulation Factor ◽  
Plasma Kallikrein ◽  
Proteolytic Activation ◽  
Factor Xia ◽  
Hepatocyte Growth
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