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.

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.

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.

scholarly journals Amelioration of Pulmonary Emphysema by In Vivo Gene Transfection With Hepatocyte Growth Factor in Rats

Circulation ◽  
2005 ◽  
Vol 111 (11) ◽  
pp. 1407-1414 ◽  
Author(s):  
Norihisa Shigemura ◽  
Yoshiki Sawa ◽  
Shinya Mizuno ◽  
Masamichi Ono ◽  
Mitsunori Ohta ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Pulmonary Emphysema ◽  
Gene Transfection ◽  
Hepatocyte Growth

scholarly journals First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients

2020 ◽  
Vol 12 ◽  
pp. 175883592092679
Author(s):  
Seung Tae Kim ◽  
Jung Yong Hong ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
Young Whan Park ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Phase I ◽  
Cancer Patients ◽  
Phase I Trial ◽  
Maximum Tolerated Dose ◽  
Safety And Efficacy ◽  
Hepatocyte Growth

Background: YYB101, a humanized monoclonal antibody against hepatocyte growth factor (HGF), has shown safety and efficacy in vitro and in vivo. This is a first-in-human trial of this antibody. Materials and Methods: YYB101 was administered intravenously to refractory cancer patients once every 4 weeks for 1 month, and then once every 2 weeks until disease progression or intolerable toxicity, at doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were studied. HGF, MET, PD-L1, and ERK expression was evaluated for 9 of 17 patients of the expansion cohort (20 mg/kg). Results: In 39 patients enrolled, no dose-limiting toxicity was observed at 0.3 mg/kg, and the most commonly detected toxicity was generalized edema ( n = 7, 18.9%) followed by pruritis and nausea ( n = 5, 13.5%, each), fatigue, anemia, and decreased appetite ( n = 4, 10.8%, each). No patient discontinued treatment because of adverse events. YYB101 showed dose-proportional pharmacokinetics up to 30 mg/kg. Partial response in 1 (2.5%) and stable disease in 17 (43.5%) were observed. HGF, MET, PD-L1, and ERK proteins were not significant predictors for treatment response. However, serum HGF level was significantly lowered in responders upon drug administration. RNA sequencing revealed a mesenchymal signature in two long-term responders. Conclusion: YYB101 showed favorable safety and efficacy in patients with refractory solid tumors. Based on this phase I trial, a phase II study on the YYB101 + irinotecan combination in refractory metastatic colorectal cancer patients is planned. Conclusion: ClinicalTrials.gov Identifier: NCT02499224

Protamine enhances the proliferative activity of hepatocyte growth factor in rats

1998 ◽  
Vol 274 (1) ◽  
pp. G21-G28 ◽  
Author(s):  
Ke-Xin Liu ◽  
Yukio Kato ◽  
Tai-Ichi Kaku ◽  
Kunio Matsumoto ◽  
Toshikazu Nakamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Proliferative Activity ◽  
Plasma Clearance ◽  
Mitogenic Response ◽  
Enhancing Effect ◽  
A Cell ◽  
Hepatocyte Growth

The effect of protamine on the proliferative activity of hepatocyte growth factor (HGF) was examined in α-naphthyl isothiocyanate-intoxicated rats. Protamine preinjection increased the hepatocyte labeling index induced by HGF four- to fivefold. A similar effect was also observed in partially hepatectomized rats. Because a cell surface heparin-like substance can bind to HGF and protamine has an affinity for heparin, protamine may affect HGF pharmacokinetics. In fact, protamine injection caused a transient increase in plasma HGF concentrations after administration of HGF and, in vitro, protamine eluted HGF prebound to heparin-Sepharose. Protamine also reduced the plasma clearance of HGF and increased 2.5-fold the exposure of hepatocytes to HGF in vivo. The enhancing effect of protamine on the mitogenic response of hepatocytes to HGF was also observed in vitro (∼2-fold after protamine pretreatment compared with HGF alone), suggesting that the enhancing effect of protamine on HGF-induced liver regeneration results from dual effects exerted by protamine 1) lowering the overall elimination of HGF and 2) directly stimulating hepatocyte mitosis induced by HGF.

Enhancement of retrovirus-mediated gene transfer to rat liver in vivo by infusion of hepatocyte growth factor and triiodothyronine

2000 ◽  
Vol 33 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Hisaka Minami ◽  
Kouji Tada ◽  
Namita Roy Chowdhury ◽  
Jayanta Roy Chowdhury ◽  
Morikazu Onji
Keyword(s):  
Growth Factor ◽  
Gene Transfer ◽  
Hepatocyte Growth Factor ◽  
Rat Liver ◽  
Hepatocyte Growth
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