Satellite cell activation in stretched skeletal muscle and the role of nitric oxide and hepatocyte growth factor

2006 ◽  
Vol 290 (6) ◽  
pp. C1487-C1494 ◽  
Author(s):  
Ryuichi Tatsumi ◽  
Xiaosong Liu ◽  
Antonio Pulido ◽  
Mark Morales ◽  
Tomowa Sakata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Methyl Ester ◽  
Hepatocyte Growth Factor ◽  
Satellite Cells ◽  
Brdu Incorporation ◽  
Dependent Manner ◽  
Hepatocyte Growth

In the present study, we examined the roles of hepatocyte growth factor (HGF) and nitric oxide (NO) in the activation of satellite cells in passively stretched rat skeletal muscle. A hindlimb suspension model was developed in which the vastus, adductor, and gracilis muscles were subjected to stretch for 1 h. Satellite cells were activated by stretch determined on the basis of 5-bromo-2′-deoxyuridine (BrdU) incorporation in vivo. Extracts from stretched muscles stimulated BrdU incorporation in freshly isolated control rat satellite cells in a concentration-dependent manner. Extracts from stretched muscles contained the active form of HGF, and the satellite cell-activating activity could be neutralized by incubation with anti-HGF antibody. The involvement of NO was investigated by administering nitro-l-arginine methyl ester (l-NAME) or the inactive enantiomer NG-nitro-d-arginine methyl ester HCl (d-NAME) before stretch treatment. In vivo activation of satellite cells in stretched muscle was not inhibited by d-NAME but was inhibited by l-NAME. The activity of stretched muscle extract was abolished by l-NAME treatment but could be restored by the addition of HGF, indicating that the extract was not inhibitory. Finally, NO synthase activity in stretched and unstretched muscles was assayed in muscle extracts immediately after 2-h stretch treatment and was found to be elevated in stretched muscle but not in stretched muscle from l-NAME-treated rats. The results of these experiments demonstrate that stretching muscle liberates HGF in a NO-dependent manner, which can activate satellite cells.

Intrinsic, extrinsic and environmental regulation of muscle satellite cell motility

2011 ◽  
Author(s):  
◽  
Ashley Lynn Siegal
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Motility ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Tibialis Anterior Muscle ◽  
Repulsive Interaction ◽  
Myogenic Stem Cells ◽  
Hepatocyte Growth

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Skeletal muscle repair and regeneration requires the activity of satellite cells, a population of myogenic stem cells. Previously, little data existed on the motility of satellite cells a critical component to tissue repair. Using timelapse videomicroscopy to assess satellite cell motility on the surface of single living myofibers, we have identified a requirement for the laminin-binding integrin a7b1 in satellite cell motility, as well as a role for hepatocyte growth factor in promoting directional persistence. We also observed more persistent long-term contact, potential cell-cell attractive and repulsive interaction, and migration between host myofibers. We found that satellite cells express multiple members of each of the four major families of guidance molecules. Satellite cell migration in vivo may be more extensive than currently thought, and could be regulated by combinations of signals including adhesive haptotaxis, soluble factors, and guidance cues. CXCL12/SDF-1 and hepatocyte growth factor/scatter factor (HGF) are included in these released factors satellite cell displacement and velocity and chemotaxis were quantified. Purified HGF and SDF-1a were injected into the Tibialis Anterior muscle (TA) to test the sufficiency of these factors for satellite cell movement in vivo. A better understanding of how satellite cells actually respond to an injury in a healthy muscle and if they are mobilized and motile from a distance will be critical to knowing if they can be induced to move through damaged or diseased muscle tissue.

Hepatocyte growth factor activates quiescent skeletal muscle satellite cells in vitro

1995 ◽  
Vol 165 (2) ◽  
pp. 307-312 ◽  
Author(s):  
Ronald E. Allen ◽  
Shannon M. Sheehan ◽  
Richard G. Taylor ◽  
Teresa L. Kendall ◽  
Glenna M. Rice
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Satellite Cells ◽  
Muscle Satellite Cells ◽  
Skeletal Muscle Satellite Cells ◽  
Hepatocyte Growth

scholarly journals Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Deborah Morena ◽  
Nicola Maestro ◽  
Francesca Bersani ◽  
Paolo Emanuele Forni ◽  
Marcello Francesco Lingua ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Satellite Cells ◽  
Critical Role ◽  
Embryonal Rhabdomyosarcoma ◽  
Dependent Manner ◽  
Wild Type ◽  
Pleomorphic Sarcoma ◽  
Human Counterpart ◽  
Hepatocyte Growth

Embryonal Rhabdomyosarcoma (ERMS) and Undifferentiated Pleomorphic Sarcoma (UPS) are distinct sarcoma subtypes. Here we investigate the relevance of the satellite cell (SC) niche in sarcoma development by using Hepatocyte Growth Factor (HGF) to perturb the niche microenvironment. In a Pax7 wild type background, HGF stimulation mainly causes ERMS that originate from satellite cells following a process of multistep progression. Conversely, in a Pax7 null genotype ERMS incidence drops, while UPS becomes the most frequent subtype. Murine EfRMS display genetic heterogeneity similar to their human counterpart. Altogether, our data demonstrate that selective perturbation of the SC niche results in distinct sarcoma subtypes in a Pax7 lineage-dependent manner, and define a critical role for the Met axis in sarcoma initiation. Finally, our results provide a rationale for the use of combination therapy, tailored on specific amplifications and activated signaling pathways, to minimize resistance emerging from sarcomas heterogeneity.

scholarly journals Serum APOA4 Pharmacodynamically Represents Administered Recombinant Human Hepatocyte Growth Factor (E3112)

2021 ◽  
Vol 22 (9) ◽  
pp. 4578
Author(s):  
Sotaro Motoi ◽  
Mai Uesugi ◽  
Takashi Obara ◽  
Katsuhiro Moriya ◽  
Yoshihisa Arita ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Disease Model ◽  
Human Hepatocytes ◽  
Dependent Manner ◽  
Protein Levels ◽  
Murine Liver ◽  
Hepatocyte Growth

Background: Hepatocyte growth factor (HGF) is an endogenously induced bioactive molecule that has strong anti-apoptotic and tissue repair activities. In this research, we identified APOA4 as a novel pharmacodynamic (PD) marker of the recombinant human HGF (rh-HGF), E3112. Methods: rh-HGF was administered to mice, and their livers were investigated for the PD marker. Candidates were identified from soluble proteins and validated by using human hepatocytes in vitro and an animal disease model in vivo, in which its c-Met dependency was also ensured. Results: Among the genes induced or highly enhanced after rh-HGF exposure in vivo, a soluble apolipoprotein, Apoa4, was found to be induced by rh-HGF in the murine liver. By using primary cultured human hepatocytes, the significant induction of human APOA4 was observed at the mRNA and protein levels, and it was inhibited in the presence of a c-Met inhibitor. Although mice constitutively expressed Apoa4 mRNA in the small intestine and the liver, the liver was the primary organ affected by administered rh-HGF to strongly induce APOA4 in a dose- and c-Met-dependent manner. Serum APOA4 levels were increased after rh-HGF administration, not only in normal mice but also in anti-Fas-induced murine acute liver failure (ALF), which confirmed the pharmacodynamic nature of APOA4. Conclusions: APOA4 was identified as a soluble PD marker of rh-HGF with c-Met dependency. It should be worthwhile to clinically validate its utility through clinical trials with healthy subjects and ALF patients.

scholarly journals In Vivo Gene Transfer of Hepatocyte Growth Factor to Skeletal Muscle Prevents Changes in Rat Kidneys After 5/6 Nephrectomy

2002 ◽  
Vol 2 (9) ◽  
pp. 828-836 ◽  
Author(s):  
Toshiyuki Tanaka ◽  
Naotsugu Ichimaru ◽  
Shiro Takahara ◽  
Koji Yazawa ◽  
Motoaki Hatori ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Gene Transfer ◽  
Hepatocyte Growth Factor ◽  
Hepatocyte Growth ◽  
In Vivo Gene Transfer ◽  
Rat Kidneys

Hepatocyte growth factor is involved in the morphogenesis of tooth germ in murine molars

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1243-1251 ◽  
Author(s):  
M.J. Tabata ◽  
K. Kim ◽  
J.G. Liu ◽  
K. Yamashita ◽  
T. Matsumura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tooth Germ ◽  
Brdu Incorporation ◽  
Histological Structure ◽  
Translation Arrest ◽  
Dental Papilla ◽  
Abnormal Structure ◽  
Hepatocyte Growth

The patterns of gene expression for hepatocyte growth factor (HGF) and its receptor, c-Met, were revealed in the tooth germ of rat mandibular molars using RT-PCR. In situ hybridization demonstrated that the HGF gene was expressed only in the cells of the dental papilla of the tooth germ in vivo. The characteristic temporospatial distribution of HGF and c-Met during germ development was revealed using immunohistochemical studies in vivo. In order to demonstrate the functional role played by HGF in tooth development, HGF translation arrest by antisense phosphorothioate oligodeoxynucleotide (ODN) was carried out in vitro. In the control experiment, explants of tooth germs from embryonic 14 day mice were cultured in a modification of Trowell's system under serum-free and chemically defined conditions for two weeks. Other explants were cultured with 15mer antisense or sense ODN targeted to the HGF mRNA. Both the control and the sense-treated explants showed normal histological structure, as observed in vivo. On the other hand, antisense-treated explants exhibited an abnormal structure in which the enamel organs were surrounded by a thin layer of dentin and dental papilla, appearing ‘inside-out’ compared to the control and sense-treated explants, although the cytodifferentiation of ameloblasts and odontoblasts was not inhibited. The explants treated with recombinant human HGF combined with antisense ODN showed normal development, indicating that exogenous HGF rescued the explants from the abnormal structure caused by antisense ODN. The findings of a BrdU incorporation experiment suggested that the imbalance between the proliferation activity of the inner enamel epithelium and that of the dental papilla caused by HGF translation arrest results in the abnormal structure of the tooth germ. These results indicate that HGF is involved in the morphogenesis of the murine molar.

Hepatocyte growth factor affects satellite cell activation and differentiation in regenerating skeletal muscle

2000 ◽  
Vol 278 (1) ◽  
pp. C174-C181 ◽  
Author(s):  
Kristy J. Miller ◽  
Deepa Thaloor ◽  
Sarah Matteson ◽  
Grace K. Pavlath
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Satellite Cell ◽  
Cell Activation ◽  
Inhibitory Effect ◽  
Satellite Cell Activation ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) is the only known growth factor that activates quiescent satellite cells in skeletal muscle. We hypothesized that local delivery of HGF may enhance regeneration after trauma by increasing the number of myoblasts available for restoring normal tissue architecture. Injection of HGF into muscle at the time of injury increases myoblast number but does not enhance tissue repair as determined using quantitative histological analyses. Rather, depending on the dose and the timing of HGF administration relative to the injury, regeneration can be inhibited. The greatest inhibitory effect is observed when HGF is administered on the day of injury and continued for 3 days, corresponding to the time when satellite cell activation, proliferation, and early differentiation normally occur. To establish a mechanism for this inhibition, we show that HGF can act directly on primary muscle cells to block differentiation. These results demonstrate that 1) exogenous HGF synergizes with factors in damaged muscle to increase myoblast number, 2) regeneration is not regulated solely by myoblast number, and 3) HGF inhibits muscle differentiation both in vitro and in vivo.

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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