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 In vivo priming of human mesenchymal stem cells with hepatocyte growth factor–engineered mesenchymal stem cells promotes therapeutic potential for cardiac repair

2020 ◽  
Vol 6 (13) ◽  
pp. eaay6994 ◽  
Author(s):  
Bong-Woo Park ◽  
Soo-Hyun Jung ◽  
Sanskrita Das ◽  
Soon Min Lee ◽  
Jae-Hyun Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Therapeutic Potential ◽  
Cardiac Repair ◽  
Vascular Regeneration ◽  
Cardiac Patch ◽  
Hepatocyte Growth

The clinical use of human bone marrow–derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)–induced hearts through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.

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

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

T1773 Adenosine Inhibits Hepatocyte Growth Factor Induced Chemotaxis in Mesenchymal Stem Cells

2008 ◽  
Vol 134 (4) ◽  
pp. A-819
Author(s):  
Mehdi Mohamadnejad ◽  
Muhammad A. Sohail ◽  
Eugene S. Swenson ◽  
Wajahat Z. Mehal
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Hepatocyte Growth

Abstract 1340: Disruption of a Hepatocyte Growth Factor/c-Met Receptor Autocrine Loop Severely Impairs the Potency of Pluripotent Adipose Stromal Cells

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Liying Cai ◽  
Brian H Johnstone ◽  
Zhong Liang ◽  
Dmitry Traktuev ◽  
Todd G Cook ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Rank Order ◽  
Residual Activity ◽  
Autocrine Loop ◽  
Major Mode ◽  
Factor C ◽  
Hepatocyte Growth

Background Paracrine stimulation of endogenous repair, rather than direct tissue regeneration, is increasingly accepted as a major mode of therapeutic stem and progenitor cell action; yet, this principle has not been fully established in vivo . Adipose-derived stem cells (ASCs) secrete many factors and promote reperfusion and tissue repair in ischemia models. RNA interference was used to silence the expression of the abundant protein, hepatocyte growth factor (HGF), to determine its contribution to ASC potency in vivo . Methods and Results Dual-cassette lentiviral vectors, expressing GFP and either a small hairpin RNA (shRNA) specific for HGF mRNA (shHGF) or a control sequence (shCtrl), were used to stably transduce ASCs (ASC-shHGF or ASC-shCtrl). ASC-shHGF secreted 5-fold less HGF, which resulted in a reduced ability of these cells to promote survival, proliferation and migration of mature and progenitor endothelial cells in vitro ( p <0.01). HGF knockdown also severely impaired the ability of ASCs to promote reperfusion in a mouse hindlimb ischemia model. Perfusion of the ischemic leg at 15 d in mice treated with ASC-Ctrl was 84±4%, compared to only 69±5% for ASC-shHGF ( p <0.05). Even so, ASC-shHGF retained residual activity as indicated by greater reperfusion ( p <0.05) than with saline treatment (58±6%). Capillary densities in ischemic tissues from each group followed a similar rank order (ASC-Ctrl>ASC-shHGF>saline) ( p <0.05 between each group). While there was no difference in total GFP + cells in ischemic limbs at 5 d after infusion, indicating similar homing potentials, 3-fold fewer ASC-shHGF were present in ischemic tissues at 15 d compared to ASC-shCtrl ( p <0.01). This was accompanied by an increase in TUNEL-positive ASC-shHGF cells (61 ± 0.1%) compared to ASC-Ctrl (41% ± 3.2%) in ischemic tissues at 5 d ( p <0.01); suggesting that attenuated potency of ASC-shHGF was related to reduced survival in ischemic tissues. Conclusions These results indicate that secretion of HGF is critically important for ASC potency. In addition to promoting endogenous repair, the data suggest that an important effect of HGF is autocrine promotion of ASC survival in ischemic tissue. Enhanced donor cell survival is an important goal for increasing the efficacy of cell therapy.

Sign in / Sign up

Export Citation Format

Share Document