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PubMed2004

Antimetastatic effect of prodigiosin through inhibition of tumor invasion.

Prodigiosin, a bacterial metabolite, was reported to have immunosuppressive and anticancer activities. In this study, we investigated novel functions of prodigiosin about anti-metastasis and anti-invasion. Prodigiosin dose-dependently inhibited 95-D cells' migration and invasion according to wound healing assay and the Transwell assay. The inhibitive effect could reach about 50% when cells were treated with 5 microM prodigiosin for 12 h. In animal experiment, intraperitoneal administration of 5 mg kg(-1) prodigiosin decreased the number of metastatic nodules by 53% and elevated the survival rate of mice about one-fold comparing with control group. Results of cell aggregation and adhesion assay showed that prodigiosin could promote cell aggregation and simultaneously inhibit cell from adhering to extracellular matrix (ECM). In addition, prodigiosin suppressed RhoA gene expression, hence, decreased protein level of RhoA in 95-D cells, according to RT-PCR assay and Western blot assay. Gel zymogram assay revealed that prodigiosin could suppress the activity of matrix metalloproteinase-2 (MMP-2). These results demonstrate that prodigiosin effectively inhibit tumor metastasis in vitro and in vivo. The action mechanisms of prodigiosin are associated with the promotion of cell aggregation and the inhibition of various steps in cell invasive process, which include the inhibition of cell adhesion and mobility in a RhoA-dependent way and the suppression of MMP-2 ability.

Animals↗
PubMed2006

Albumin-derived nanocarriers: substrates for enhanced cell adhesive ligand display and cell motility.

Cell-adhesive ligands organized on nanoscale synthetic biomaterials can potentially recapitulate the nanoscale organization of extracellular matrix and the consequent effects of cell dynamics. In this study, 100 nm albumin nanocarriers (ANC) were fabricated to serve as nanoscale organizational units for a well-defined ligand, the recombinant fragment from fibronectin comprised of the RGD-containing module 10 and the synergy-region-containing module 9. Conventional protein conjugation chemistry was employed to fabricate nanocarriers with increasing levels of displayed ligand. Presentation of ligand-functionalized ANCs adsorbed onto substrates was found to enhance keratinocyte attachment when compared to equivalent levels of adsorbed ligands, supported by ELISA data that the display of ligand on ANCs essentially increased the accessibility of the cell-binding domain and AFM data that the ligand was likely exposed due to ligand-ANC repulsion. The ligand presentation from ANCs converted the cellular morphology from a stationary phenotype to a motile phenotype, with the expression of filopodia-like microextensions, and a decrease in focal adhesions, indicating decreased cell adhesion strength. Consequently, cell motility was found to be significantly elevated on ligand-ANC substrates relative to substrates with equivalent levels of ligand. Overall, the ligand-functionalized albumin nanocarriers offer a unique model platform with two distinct properties: enhanced ligand exposure for enhancement of cell attachment to ligands at low concentrations; and enhanced cell detachment, motile phenotype, and migration kinetics.

Biocompatible Materials↗
PubMed2001

Insulin resistance and cardiovascular disease.

Cardiovascular risk factors cluster in obese individuals. Insulin resistance emerges as a common pathogenetic denominator underlying the risk factor cluster. Defects in nonesterified fatty acids metabolism have been implicated in the abnormal lipid and glucose metabolism which characterize the cluster. Other evidence also leads to the adipocyte as an important contributor to the risk factor cluster and cardiovascular complications through effects not only on fatty acids but also on leptin, plasminogen activator inhibitor-1, and angiotensinogen, to name a few. Fatty acids are elevated among abdominally obese individuals, are more resistant to suppression by insulin, and may contribute to hypertension. Fatty acids may affect blood pressure by inhibiting endothelial nitric oxide synthase activity and impairing endothelium-dependent vasodilation. Fatty acids increase alpha1-adrenoceptor-mediated vascular reactivity and enhance the proliferation and migration of cultured vascular smooth-muscle cells. Several effects of fatty acids are mediated through oxidative stress. Fatty acids can also interact with other facets of cluster, including increased angiotensin II, to accentuate oxidative stress. Oxidative stress, in turn, is implicated in the pathogenesis of insulin resistance, hypertension, vascular remodeling, and vascular complications. A clearer delineation of the key reactive oxygen signaling pathways and the impact of various interventions on these pathways could facilitate a rationale approach to antioxidant therapy and improved outcomes among the rapidly growing number of high-risk, insulin-resistant, obese individuals.

Cardiovascular Diseases↗
PubMed2000

Macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and RANTES mRNA semiquantification and protein expression in active demyelinating multiple sclerosis (MS) lesions.

MS is a demyelinating disease characterized by infiltration of monocytes and lymphocytes into the brain parenchyma, destruction of oligodendrocytes and loss of myelin. Since chemokines play a major role in the migration of monocytes and T cells, we here investigated the expression of the CC chemokines MIP-1alpha, MIP-1beta, and RANTES in brain tissue from MS patients using reverse transcriptase-polymerase chain reaction techniques. Both MIP-1beta as well as RANTES were found to be significantly elevated in brain tissue of MS patients. In addition, MIP-1alpha was also increased, although not significantly. Immunohistochemistry revealed that, whereas RANTES was mainly localized in reactive astrocytes, MIP-1alpha and MIP-1beta immunoreactivity was predominantly found in perivascular and parenchymal macrophages, containing myelin degradation products. Thus, chemokines appear to be associated with MS and an increased chemokine expression may further enhance disease progression by attracting more leucocytes into the brain parenchyma and by activation of effector functions of astrocytes and microglial cells.

Adult↗
PubMed2003

Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination.

Pten is a tumor suppressor gene mutated in human cancers. We used the Cre-loxP system to generate a B cell-specific mutation of Pten in mice (bPten(flox/flox)mice). bPten(flox/flox) mice showed elevated numbers of B1a cells and increased serum autoantibodies. Among B2 cells in bPten(flox/flox) spleens, numbers of marginal zone B (MZB) cells were significantly increased while those of follicular B (FOB) cells were correspondingly decreased. Pten-deficient B cells hyperproliferated, were resistant to apoptotic stimuli, and showed enhanced migration. The survival kinase PKB/Akt was highly activated in Pten-deficient splenic B cells. In addition, immunoglobulin class switch recombination was defective and induction of activation-induced cytidine deaminase (AID) was impaired. Thus, Pten plays a role in developmental fate determination of B cells and is an indispensable regulator of B cell homeostasis.

Animals↗
PubMed1999

Antibody-dependent reductions in mouse hookworm burden after vaccination with Ancylostoma caninum secreted protein 1.

Vaccination of mice with either third-stage Ancylostoma caninum infective hookworm larvae (L3) or alum-precipitated recombinant Ancylostoma secreted protein 1 from A. caninum (Ac-ASP-1) results in protection against hookworm challenge infections. Vaccine protection is manifested by reductions in lung hookworm burdens at 48 h postchallenge. Mice actively immunized 4 times with Ac-ASP-1 also exhibited reductions in hookworm burden in the muscles. Hookworm burden reductions from Ac-ASP-1 immunization were associated with elevations in all immunoglobulin subclasses, with the greatest rise observed in host IgG1 and IgG2b. The addition of a fourth immunization resulted in even higher levels of IgG and IgE. In contrast, L3-vaccinated mice exhibited marked elevations in IgG1 and IgM, including anti-Ac-ASP-1 IgM antibody. Passive immunization with pooled sera from recombinant Ac-ASP-1-vaccinated mice also resulted in lung hookworm burden reductions. It is hypothesized that recombinant Ac-ASP-1 vaccinations elicit antibody that interferes with parasite larval migration.

Ancylostoma↗
PubMed2005

Dose dependent and divergent effects of superoxide anion on cell death, proliferation, and migration of activated human hepatic stellate cells.

BACKGROUND AND AIMS: Activated myofibroblast-like cells, originating from hepatic stellate cells (HSC/MFs) or other cellular sources, play a key profibrogenic role in chronic liver diseases (CLDs) that, as suggested by studies in animal models or rat HSC/MFs, may be modulated by reactive oxygen intermediates (ROI). In this study, human HSC/MFs, exposed to different levels of superoxide anion (O(2)(.-)) and, for comparison, hydrogen peroxide (H(2)O(2)), were analysed in terms of cytotoxicity, proliferative response, and migration. METHODS: Cultured human HSC/MFs were exposed to controlled O(2)(.-) generation by hypoxanthine/xanthine oxidase systems or to a range of H(2)O(2) concentrations. Induction of cell death, proliferation, and migration were investigated using morphology, molecular biology, and biochemical techniques. RESULTS: Human HSC/MFs were shown to be extremely resistant to induction of cell death by O(2)(.-) and only high rates of O(2)(.-) generation induced either necrotic or apoptotic cell death. Non-cytotoxic low levels of O(2)(.-), able to upregulate procollagen type I expression (but not tissue inhibitor of metalloproteinase 1 and 2), stimulated migration of human HSC/MFs in a Ras/extracellular regulated kinase (ERK) dependent, antioxidant sensitive way, without affecting basal or platelet derived growth factor (PDGF) stimulated cell proliferation. Non-cytotoxic levels of H(2)O(2) did not affect Ras/ERK or proliferative response. A high rate of O(2)(.-) generation or elevated levels of H(2)O(2 )induced cytoskeletal alterations, block in motility, and inhibition of PDGF dependent DNA synthesis. CONCLUSIONS: Low non-cytotoxic levels of extracellularly generated O(2)(.-) may stimulate selected profibrogenic responses in human HSC/MFs without affecting proliferation.

Apoptosis↗
PubMed1993

Hormones and growth factors in germ cell neoplasia: general discussion.

Fetal germ cells migrate along the dorsal mesentery to the genital ridge, and migration in the bloodstream occurs in some animals. Malignant transformation may occur before migration, and it is possible that testicular germ cell tumours have a monoclonal origin, even when bilateral. Different tumour foci have homogeneous chromosomal abnormalities. Migrating germ cells may lodge in extragonadal sites and give rise to tumours. Mouse fetuses exposed to oestrogen and testosterone in utero have an increased incidence of testicular maldescent and teratoma. Oestrogens and mullerian inhibitory substance in the fetus may influence human testicular tumour development. Testicular tumour patients may have elevated serum oestrogen levels which may be related to prognosis. Increased serum FSH may stimulate germ cell tumour growth. Ultrastructural studies indicate that malignant transformation of germ cells occurs early, but final tumour differentiation does not occur till after the malignant cells have invaded extratubular tissue.

Animals↗
PubMed1996

Identification of the major chemokines that regulate cell influxes in peritoneal dialysis patients.

To investigate which members of the recently discovered family of chemotactic cytokines (chemokines) are important in leukocyte recruitment to a bacterial inflammation site, four different chemokines in the effluent of peritoneal dialysis patients suffering from acute bacterial peritonitis were measured. The presence of two neutrophil-attracting chemokines, interleukin-8 and human melanoma growth-stimulating activity (huGRO alpha), and two monocyte-attracting members of the chemokine superfamily, monocyte chemotactic protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES), was investigated in patient effluents just before, during, and after a peritonitis episode. This was studied in seven peritonitis effluents of five patients by using chemokine-specific enzyme-linked immunosorbent assays. Cell populations in the dialysates were differentiated on cytocentrifuge preparations. The contribution of the detected chemokines to neutrophilic and monocytic cell influxes in the inflamed peritoneal cavity was analyzed by correlating concentrations of chemokines to the relevant cell numbers present in the dialysates of these patients. The detection of the neutrophil-attracting chemokine interleukin-8 during peritonitis was in accordance with other studies. Moreover, a second neutrophil chemoattractant, huGRO alpha, was identified in vivo. Both were elevated during inflammation (P < 0.02) and contributed significantly to the neutrophilic cell influx (P < 0.05). One of the monocyte-attracting chemokines, RANTES, could not be detected in any of the effluents, whereas the other, MCP-1, was significantly elevated during peritonitis (P < 0.02). In contrast to the other chemokines measured, MCP-1 concentration was relatively high in steady-state peritoneal dialysates. An absolute correlation between dialysate MCP-1 concentration and the number of macrophages in these effluents was absent. However, in a 48-well chemotaxis assay, monocyte migration toward peritonitis, as well as steady-state patient dialysates, could be blocked with antibodies to MCP-1. It was concluded, therefore, that MCP-1 is the most important monocyte chemoattractant in peritoneal dialysis steady-state and peritonitis patients; whereas, besides interleukin-8, huGRO alpha was identified as a major neutrophil-attracting chemokine in the peritonitis situation.

Acute Disease↗
PubMed1988

The role of inflammation in the development of epiretinal membranes.

Single or multiple (3) injections of "Shigella" endotoxin were administered into the rabbit vitreous body to investigate the development of epiretinal membranes following intraocular inflammation. The evaluation included clinical assessment of the resulting traction retinal detachments, together with histological, autoradiographic, immunohistochemical and ultrastructural studies. Traction retinal detachments were found beneath fibroglial epiretinal membranes (being more extensive in eyes which had received 3 endotoxin injections) in the vicinity of the medullary rays, while purely glial membranes occurred over attached peripheral retina. The primary change at the vitreoretinal interface was an elevation of the inner limiting lamina of the retina followed by the extension of glial cells onto the retinal surface. It is postulated that glial cells breach the inner limiting lamina as a sequel to inflammation involving the vitreoretinal interface and form a scaffold upon which fibroblast-like cells migrate.

Animals↗
PubMed2006

Akt/PKB signaling in cancer: a function in cell motility and invasion.

The PI 3-K signaling pathway has been the subject of intense investigation for over a decade because it regulates a multitude of cellular processes. Deregulation of this pathway often results in human diseases such as cancer. The serine/threonine kinase Akt, a major PI 3-K target in all cells, has received considerable attention because it provides tumor cells with enhanced survival capacity. Many tumors and tumor cells display elevated Akt protein expression and activity, and many of the proteins which regulate Akt itself are also often mutated in cancer. For this reason, Akt has become a viable drug target for cancer therapy. However, recent studies have shown that Akt can also function as a suppressor of tumor cell migration and invasion, phenotypes which are directly linked to metastatic tumor progression. Here we review these findings and consider the unexpected notion that Akt may function as a metastasis suppressor.

Animals↗
PubMed2006

Blockade of endothelin-1 release contributes to the anti-angiogenic effect by pro-opiomelanocortin overexpression in endothelial cells.

Pro-opiomelanocortin (POMC) is the precursor of several neuropeptides, such as corticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and the endogenous opioid, beta-endorphin (EP). ACTH-dependent Cushing's syndrome is characterized by ACTH overproduction and is associated with an increased risk of cardiovascular disease. Endothelial dysfunction has been recognized as an early marker of cardiovascular disease. However, the mechanism underlying endothelial dysfunction by ACTH overexpression in Cushing's patients remains elusive. Endothelial cells, the primary cells producing endothelin (ET)-1, are both the source and target of POMC-derived peptides. In the present study, we generated adenovirus vectors (Ad) encoding POMC (Ad-POMC) and green fluorescent protein (GFP; Ad-GFP) to investigate whether POMC gene transfer altered the ET-1 homeostasis and angiogenic functions in human EA.hy926 endothelial cells. Via adenovirus gene delivery, the POMC-transduced EA.hy926 cells released significantly elevated ACTH and beta-EP levels (P < 0.001). In addition, POMC gene delivery significantly decreased the ET-1 release (P < 0.001) without affecting the ET-1 messenger RNA (mRNA) level. Despite no effect on the secretion of matrix metalloproteinases (MMPs) and cell proliferation, POMC gene delivery significantly inhibited the migration (P < 0.01) and tube-forming capability (P < 0.01) of endothelial cells. Moreover, the POMC-induced inhibition of tube formation could be partially reversed by adding exogenous ET-1 (P < 0.05). In summary, the attenuated ET-1 release and angiogenic processes by POMC overexpression may contribute to endothelial dysfunction, thereby providing a link between Cushing's syndrome and cardiovascular diseases.

Adenoviridae↗
PubMed1994

A peptide derived from the amino terminus of endothelial-monocyte-activating polypeptide II modulates mononuclear and polymorphonuclear leukocyte functions, defines an apparently novel cellular interaction site, and induces an acute inflammatory response.

Endothelial-monocyte-activating polypeptide II (EMAP II) is a novel mediator isolated from conditioned medium of methylcholanthrene A-induced tumor cells which modulates properties of endothelial cells, mononuclear phagocytes (MPs), and polymorphonuclear leukocytes (PMNs) in vitro and induces an acute inflammatory response in vivo. A synthetic peptide comprising 15 residues from the N-terminal region (residues 6-20) was shown to induce directional migration of MPs and PMNs, with half-maximal effect at approximately 200-250 pM, whereas a peptide from the C terminus of EMAP II, as well as other irrelevant peptides, were without effect. Modulation of cellular phenotype by EMAP II-derived peptide was suggested by peptide-induced elevation of cytosolic free calcium concentration in fura-2-loaded MPs and PMNs and by stimulation of peroxidase release in PMNs. Consistent with these in vitro data, EMAP II-derived N-terminal peptide-albumin conjugates injected into the mouse footpad elicited inflammatory cell tissue infiltration, whereas albumin alone or EMAP II-derived C-terminal peptide conjugated to albumin incited little response. Binding of 125I-labeled EMAP II-derived peptide (residues 12-20) to MPs was saturable (Kd approximately 200 pM) and was blocked in a dose-dependent manner by the addition of intact EMAP II and unlabeled EMAP II-derived peptides (residues 6-20 and 12-20), whereas interleukin 1, tumor necrosis factor, formyl-methionyl-leucinyl-phenylalanine, or irrelevant peptides were without effect. Cross-linking of 125I-EMAP II-derived peptide (residues 12-20) by disuccinimidyl suberate to human MPs demonstrated a band, approximately 73 kDa, on reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 125I-EMAP II-derived peptide also demonstrated specific binding to human PMNs and murine RAW cells. These data indicate that the N-terminal region of EMAP II defines a biologically active locus of the molecule which interacts with target cells via a potentially novel cellular receptor.

Amino Acid Sequence↗
PubMed2002

Immunity to placental malaria. IV. Placental malaria is associated with up-regulation of macrophage migration inhibitory factor in intervillous blood.

Macrophage migration inhibitory factor (MIF) may play a role in immune responses to malaria during pregnancy by virtue of its ability to activate macrophages and to overcome the immunosuppressive effect of glucocorticoids. The present study investigated whether plasma MIF levels are altered in pregnant women with placental malaria (PM) and/or human immunodeficiency virus (HIV) infection. For the first time it is demonstrated that MIF levels in the intervillous blood (IVB) plasma were significantly elevated, compared with that in both peripheral plasma ( approximately 500-fold) and cord plasma (4.6-fold; P<.01). IVB mononuclear cells also produced significantly higher levels of MIF, compared with that of peripheral blood mononuclear cells. PM was associated with increased levels of MIF in the IVB plasma (P<.02). Primigravid and secundigravid women had significantly higher levels of MIF in their IVB plasma than did multigravid women (P<.05). HIV infection did not significantly alter MIF levels in any site examined.

Female↗
PubMedDate not supplied

Inbreeding coefficients and degree of consanguineous marriages in Spain: a review.

The contribution of consanguineous marriages corresponding to uncle-niece or aunt-nephew (C12), first cousin (C22), first cousin once removed (C23), and second cousin (C33) to the inbreeding coefficient (alpha) was analyzed from a sample of Spanish areas and periods. Multiple regressions were performed taking as independent variables the different degrees of consanguinity previously selected (C12, C22, C23, and C33) and as dependent variable the inbreeding coefficient (alpha). According to the results obtained for any degree and period, rural frequencies always surpass urban. However, the pattern is similar in both areas. In the period where consanguinity was more elevated (1890-1929) the C22/C33 ratio increased. Its variation is not due to C22 and C33 changes in the same way. In rural areas, this ratio surpasses the expected value by a factor of 2-3, but in urban areas it was 7-10 times larger, in some cases due to migration. While in rural Spain the C33 frequency was approximately 1.5 times C22, in cities C22 was 1.5 times C33. The best fit among the various types of consanguineous matings and alpha involves a lineal relationship. Regardless of the number of variables contributing significantly to alpha, C22 matings are always present. Moreover, their standardized (beta) coefficients are the highest. The above indicates that this consanguineous relationship conditions the inbreeding coefficient the most. In the period of greater consanguinity, close relationships, uncle-niece C12, and first cousin once removed (C23) make a significant contribution to alpha. In rural Spain second cousins (C33) always significantly determined alpha; however, in cities the inbreeding variation was mainly due to C12 and C23.

Consanguinity↗
PubMed1993

Temperature-gradient gel electrophoresis for analysis and screening of thermostable proteases.

The thermal unfolding of microbial serine proteases was studied by temperature-gradient gel electrophoresis (TGGE). Conditions for a native polyacrylamide gel electrophoresis were established, and the temperature gradient was applied perpendicularly to the direction of electrophoretic migration. Mobility changes of the protease molecules were indicative for thermally induced conformational changes. The transition temperature was determined with good accuracy. The native and active protease conformation was detected by an activity assay in the temperature-gradient gel. As a consequence of the typical protease-autoproteolytic reaction at elevated temperatures, the unfolded protease conformation could not be detected for non-inhibited, active subtilisin. After inhibition by phenylmethylsulfonyl fluoride (PMSF) the complete structural transition could be followed by TGGE. This transition is "discontinuous", i.e. the thermal transition is either very slow, compared to the time of electrophoresis, or irreversible, as known for subtilisins from calorimetric data. Inhibition by the strong serine specific inhibitor diisopropyl fluorophosphate (DFP) led to two conformations at low temperature. One conformation is stabilized by 8 degrees C, the other by at least 20 degrees C as compared with PMSF inhibition. The influence of calcium ions on the subtilisin stability was investigated by a series of TGGE under different calcium concentrations. The strong calcium binding site is occupied even without added calcium, occupation of the weak binding site leads to a stabilization of 10 degrees C with a binding constant around 10(6) M-1. The subtilisin Carlsberg stability could also be investigated in unpurified bacterial culture supernatants. Thus, the method is suitable for screening of thermostable subtilisin mutants directly after expression in a bacterial host.(ABSTRACT TRUNCATED AT 250 WORDS)

Buffers↗
PubMed2004

Is the "Lost World" really lost? Palaeoecological insights into the origin of the peculiar flora of the Guayana Highlands.

The peculiar biogeography of the so-called "Lost World", i.e. the summits of sandstone tableaux ( tepuis) in the Neotropical Guyana region of Venezuela, has generated a debate regarding the factors that are thought to account for modern vegetation patterns in the region. Some argue that plant communities on these high-elevation summits reflect a long history of evolution in isolation, while others surmise that there has been substantial biotic interchange with the surrounding lowlands during glacial times. Until now, these apparently competing hypotheses have not been tested using palaeoecological methods. I used pollen analysis of Quaternary sediments and documented past vertical migrations of vegetation in response to climate changes, which supports the second hypothesis. Physiographical analysis, however, shows that about half the tableaux summits are too high for their flora to have reached the lowlands during the last glaciation, suggesting that a portion of the tableaux vegetation has always experienced some degree of biotic isolation. Thus, a component of the summit vegetation evolved in isolation, whereas other taxa experienced interchange, as reflected in endemism patterns among the tableaux summits. Biogeographical patterns on the summits are the result of complex evolutionary processes. The two hypotheses invoked to explain the vegetation patterns are not mutually exclusive, but instead complement one another.

Altitude↗
PubMed1997

Thrombin regulates nerve growth factor secretion from vascular, but not bladder smooth muscle cells.

The production of nerve growth factor (NGF) in peripheral organs may play a role in the pathophysiology of hypertension and in obstructive disorders of the bladder outlet. We have been examining the cellular processes of NGF delivery and secretion in smooth muscle. NGF secretion from vascular smooth muscle cells (VSMCs) cultured from genetically hypertensive (WKHT), hyperactive (WKHA), and a control Wistar rat strain were assayed using a two-site ELISA of the culture media. Bladder smooth muscle cells (BSMCs) from the Wistar strain were also studied. The serine protease, thrombin, increased NGF secretion from all types of VSMCs but had no effect on Wistar BSMCs. The thrombin-mediated increase in NGF secretion was prevented by actinomycin D and cycloheximide, suggesting that RNA transcription and protein synthesis are required. The effect of thrombin was additive with a phorbol ester-induced elevation in NGF secretion rates from 4 to 6 h and was attenuated by a 24-h downregulation of protein kinase C. These results suggest that extracellular protease activity may regulate NGF secretion in smooth muscle. Thrombin may act in response to vascular injury, increasing NGF secretion from VSMCs, initiating VSMC migration, and preparing the VSMCs for reinnervation following an insult.

Animals↗