Anti-hepatocyte growth factor antibody inhibits the in vivo proliferative response of hepatocytes to acute liver injury

1995 ◽  
Vol 108 (4) ◽  
pp. A1041
Author(s):  
AW Burr ◽  
K. Toole ◽  
JE Hines ◽  
C Chapman ◽  
AD Burt
Keyword(s):  
Growth Factor ◽  
Liver Injury ◽  
Hepatocyte Growth Factor ◽  
Proliferative Response ◽  
Acute Liver Injury ◽  
Hepatocyte Growth

Retrovirus-Mediated In Vivo Gene Transfer in the Replicating Liver Using Recombinant Hepatocyte Growth Factor Without Liver Injury or Partial Hepatectomy

1998 ◽  
Vol 9 (9) ◽  
pp. 1293-1301 ◽  
Author(s):  
Ken-Ichiro Kosai ◽  
Milton J. Finegold ◽  
Bich-Thuy Thi-Huynh ◽  
Margaret Tewson ◽  
Ching-Nan Ou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gene Transfer ◽  
Liver Injury ◽  
Hepatocyte Growth Factor ◽  
Partial Hepatectomy ◽  
Hepatocyte Growth ◽  
In Vivo Gene Transfer

Suppression of acute hepatic injury by a synthetic prostacyclin agonist through hepatocyte growth factor expression

2012 ◽  
Vol 302 (4) ◽  
pp. G420-G429 ◽  
Author(s):  
Qing Xu ◽  
Mizuho Nakayama ◽  
Yoshinori Suzuki ◽  
Katsuya Sakai ◽  
Takahiro Nakamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Injury ◽  
Hepatocyte Growth Factor ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Protective Action ◽  
Liver Cells ◽  
Cyclooxygenase 2 ◽  
Peroral Administration ◽  
Hepatocyte Growth

Previous studies have demonstrated that mice disrupted with the cyclooxygenase-2 gene showed much more severe liver damage compared with wild-type mice after liver injury, and prostaglandins (PGs) such as PGE1/2 and PGI2 have decreased hepatic injury, but the mechanisms by which prostaglandins exhibit protective action on the liver have yet to be addressed. In the present study, we investigated the mechanism of the protective action of PGI2 using the synthetic IP receptor agonist ONO-1301. In primary cultures of hepatocytes and nonparenchymal liver cells, ONO-1301 did not show protective action directly on hepatocytes, whereas it stimulated expression of hepatocyte growth factor (HGF) in nonparenchymal liver cells. In mice, peroral administration of ONO-1301 increased hepatic gene expression and protein levels of HGF. Injections of CCl4 induced acute liver injury in mice, but the onset of acute liver injury was strongly suppressed by administration of ONO-1301. The increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by CCl4 were suppressed by 10 mg/kg ONO-1301 to 39.4 and 33.6%, respectively. When neutralizing antibody against HGF was administered with ONO-1301 and CCl4, the decreases by ONO-1301 in serum ALT and AST, apoptotic liver cells, and expansion of necrotic areas in liver tissue were strongly reversed by neutralization of endogenous HGF. These results indicate that ONO-1301 increases expression of HGF and that hepatoprotective action of ONO-1301 in CCl4-induced liver injury may be attributable to its activity to induce expression of HGF, at least in part. The potential for involvement of HGF-Met-mediated signaling in the hepatotrophic action of endogenous prostaglandins generated by injury-dependent cyclooxygenase-2 induction is considerable.

Downregulation of miR‐1224 protects against oxidative stress‐induced acute liver injury by regulating hepatocyte growth factor

2019 ◽  
Vol 120 (8) ◽  
pp. 12369-12375 ◽  
Author(s):  
Wenting Cheng ◽  
Guo‐pan Liu ◽  
Dehua Kong ◽  
Wei Huang ◽  
Ying Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Liver Injury ◽  
Hepatocyte Growth Factor ◽  
Acute Liver Injury ◽  
Hepatocyte Growth

CCl4 -induced acute liver injury in mice is inhibited by hepatocyte growth factor overexpression but stimulated by NK2 overexpression

FEBS Letters ◽  
2002 ◽  
Vol 532 (3) ◽  
pp. 391-395 ◽  
Author(s):  
Toshiyuki Otsuka ◽  
Hitoshi Takagi ◽  
Norio Horiguchi ◽  
Mitsuo Toyoda ◽  
Ken Sato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Injury ◽  
Hepatocyte Growth Factor ◽  
Acute Liver Injury ◽  
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.

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