The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease

2015 ◽  
Vol 45 (4) ◽  
pp. 985-1000 ◽  
Author(s):  
John W. Wright ◽  
Joseph W. Harding
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Met Receptor ◽  
Receptor System ◽  
System A ◽  
Factor C ◽  
The Brain ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF/SF) in Alzheimer's disease

1998 ◽  
Vol 779 (1-2) ◽  
pp. 262-270 ◽  
Author(s):  
H Fenton ◽  
P.W Finch ◽  
J.S Rubin ◽  
J.M Rosenberg ◽  
W.G Taylor ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Hepatocyte Growth

scholarly journals Hepatocyte Growth Factor in Synaptic Plasticity and Alzheimer's Disease

2010 ◽  
Vol 10 ◽  
pp. 457-461 ◽  
Author(s):  
Shiv K. Sharma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Receptor Tyrosine Kinase ◽  
Hippocampal Neurons ◽  
Different Types ◽  
Hepatocyte Growth

The hepatocyte growth factor (HGF) was initially identified as a protein that promoted growth of hepatocytes. It regulates proliferation and survival of different types of cells. HGF signaling, which is initiated by its binding to a receptor tyrosine kinase, plays critical roles during development. HGF and its receptor are also present in brain cells. This review describes the role of HGF in hippocampal neurons, synaptic plasticity, and the memory impairment condition, Alzheimer's disease.

scholarly journals Associations of the cerebrospinal fluid hepatocyte growth factor with Alzheimer’s disease pathology and cognitive function

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li-Jing Zhao ◽  
Zuo-Teng Wang ◽  
Ya-Hui Ma ◽  
Wei Zhang ◽  
Qiang Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cognitive Decline ◽  
Regression Models ◽  
Linear Regression Models ◽  
Mediation Effects ◽  
Hepatocyte Growth

Abstract Background Hepatocyte growth factor (HGF) plays a role in neuronal survival and development, and has been implicated in neurodegenerative diseases. We sought to examine the associations of the CSF HGF with Alzheimer’s disease (AD) pathology and cognitive function. Methods A total of 238 participants (including 90 cognitively normal (CN) and 148 mild cognitive impairment (MCI)) who had measurements of CSF HGF were included from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Multiple linear regression models were utilized to explore the cross-sectional associations of CSF HGF with AD biomarkers (including Aβ42, pTau, and tTau proteins) in non-demented participants. Moreover, linear mixed-effects regression models were utilized to explore the longitudinal associations of HGF subgroups with cognitive function. Mediation analyses were utilized to explore the mediation effects of AD markers. Results MCI individuals had significantly increased CSF HGF compared with the CN individuals. Results of multiple linear regressions showed significant correlations of CSF HGF with CSF Aβ42, pTau, and tTau in non-demented participants. Higher level of baseline CSF HGF was associated with faster cognitive decline. Influences of the baseline CSF HGF on cognition were partially mediated by Aβ42, pTau, and tTau pathologies. Conclusions High concentrations of HGF in CSF may be related to faster cognitive decline. The cognitive consequences of higher CSF HGF partly stem from AD pathology, which suggests that the CSF HGF may be an attractive biomarker candidate to track AD progression.

Hepatocyte Growth Factor and Macrophage-stimulating Protein “Hinge” Analogs to Treat Pancreatic Cancer

2019 ◽  
Vol 19 (10) ◽  
pp. 782-795
Author(s):  
John W. Wright ◽  
Kevin J. Church ◽  
Joseph W. Harding
Keyword(s):  
Pancreatic Cancer ◽  
Signal Transduction ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tumor Growth ◽  
Receptor Activation ◽  
Signal Transduction Pathways ◽  
Met Receptor ◽  
Macrophage Stimulating Protein ◽  
Hepatocyte Growth

Pancreatic cancer (PC) ranks twelfth in frequency of diagnosis but is the fourth leading cause of cancer related deaths with a 5 year survival rate of less than 7 percent. This poor prognosis occurs because the early stages of PC are often asymptomatic. Over-expression of several growth factors, most notably vascular endothelial growth factor (VEGF), has been implicated in PC resulting in dysfunctional signal transduction pathways and the facilitation of tumor growth, invasion and metastasis. Hepatocyte growth factor (HGF) acts via the Met receptor and has also received research attention with ongoing efforts to develop treatments to block the Met receptor and its signal transduction pathways. Macrophage-stimulating protein (MSP), and its receptor Ron, is also recognized as important in the etiology of PC but is less well studied. Although the angiotensin II (AngII)/AT1 receptor system is best known for mediating blood pressure and body water/electrolyte balance, it also facilitates tumor vascularization and growth by stimulating the expression of VEGF. A metabolite of AngII, angiotensin IV (AngIV) has sequence homology with the “hinge regions” of HGF and MSP, key structures in the growth factor dimerization processes necessary for Met and Ron receptor activation. We have developed AngIV-based analogs designed to block dimerization of HGF and MSP and thus receptor activation. Norleual has shown promise as tested utilizing PC cell cultures. Results indicate that cell migration, invasion, and pro-survival functions were suppressed by this analog and tumor growth was significantly inhibited in an orthotopic PC mouse model.

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.

Involvement of hepatocyte growth factor/scatter factor and Met receptor signaling in hair follicle morphogenesis and cycling

2000 ◽  
Vol 14 (2) ◽  
pp. 319-332 ◽  
Author(s):  
Gerd Lindner ◽  
Andreas Menrad ◽  
Ermanno Gherardi ◽  
Glenn Merlino ◽  
Pia Welker ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Hair Follicle ◽  
Receptor Signaling ◽  
Met Receptor ◽  
Scatter Factor ◽  
Hepatocyte Growth
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