Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the phenotype of the blood vessels and the expression of the growth factors involved in angiogenesis in metastatic liver cancers, we carried out an immunohistochemical study of 57 surgically resected livers with metastatic cancer. Blood vessels in the metastatic liver cancers frequently expressed von Willebrand factor (vWF), Ulex europaeus agglutinin I (UEA I)-binding sites, alpha-smooth muscle actin (alpha-SMA), type IV collagen and laminin. Sinusoidal endothelial cells around the metastatic liver cancers were positive for vWF in 33.3% of the specimens examined and for UEA I in 28.1%. alpha-SMA-positive perisinusoidal cells accumulated in the vicinity of the metastatic liver cancers in 68.4% of the specimens. Type IV collagen was detected in the perisinusoidal space close to the metastatic cancers as well as distant from them (91.2%). Laminin was detected in the perisinusoidal space in only one specimen (1.8%). Tumour cells of the metastatic liver cancers were positive for vascular endothelial growth factor, basic fibroblast growth factor (bFGF), and acidic fibroblast growth factor (aFGF) in 78.9%, 38.4% and 7.0% of the specimens, respectively. Hepatocytes close to the metastatic liver cancers expressed bFGF more strongly than those distant from the metastatic liver cancers, and their expression of bFGF was more intense than that in the tumour cells. These results suggest that: (1) tumour vessels in metastatic liver cancers consist of endothelium, basement membrane and pericytes, (2) the sinusoids adjacent to tumours undergo capillarization, and (3) vascular endothelial growth factor may contribute to angiogenesis in metastatic liver cancer. Basic fibroblast growth factor may be responsible for the sinusoidal capillarization and the peritumoral fibrosis.
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PMID:An immunohistochemical study of tumour vessels in metastatic liver cancers and the surrounding liver tissue. 881 92

We report a case of lymphangioma involving oral mucosa and mandible of an elderly female. The surgical and radiological examinations indicated that the lymphangioma was mainly distributed in the labial mucosa tissue, but had gradually extended into the periosteum and intrabony space of mandible. Immunohistochemical staining was also performed using antiseras of alpha-smooth muscle actin (alpha-SMA), von Willebrand factor (vWF), angiogenin, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) to elucidate the pathogenetic implications of the intraosseous lymphangioma. The present case of lymphangioma showed strong immunohistochemical reactivity of angiogenin and vWF, while it showed weak reactions of VEGF and PCNA. The immunostaining of alpha-SMA disclosed an abnormally thinned and discontinuous smooth muscle layer in the lymphatics. Both the X-rays and histological examination showed that the lymphangioma lesion was gradually extending into the adjacent osteoporotic marrow space of mandible. Therefore, we believe that the present case of intraosseous lymphangioma, which showed the harmatomatous growth of the lymphatics into the marrow space of mandible, is closely related to osteoporotic changes of old age.
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PMID:Lymphangioma involving the mandible: immunohistochemical expressions for the lymphatic proliferation. 1211 45

VEGF-A is a major angiogenesis and permeability factor. Its cellular effects, which can be used as targets in anti-angiogenesis therapy, have mainly been studied in vitro using endothelial cell cultures. The purpose of the present study was to further characterize these effects in vivo in vascular endothelial cells and pericytes, in an experimental monkey model of VEGF-A-induced iris neovascularization. Two cynomolgus monkeys (Macaca fascicularis) received four injections of 0.5 microg VEGF-A in the vitreous of one eye and PBS in the other eye. After sacrifice at day 9, eyes were enucleated and iris samples were snap-frozen for immunohistochemistry (IHC) and stained with a panel of antibodies recognizing endothelial and pericyte determinants related to angiogenesis and permeability. After VEGF-A treatment, the pre-existing iris vasculature showed increased permeability, hypertrophy, and activation, as demonstrated by increased staining of CD31, PAL-E, tPA, uPA, uPAR, Glut-1, and alphavbeta3 and alphavbeta5 integrins, VEGF receptors VEGFR-1, -2 and -3, and Tie-2 in endothelial cells, and of NG2 proteoglycan, uPA, uPAR, integrins and VEGFR-1 in pericytes. Vascular sprouts at the anterior surface of the iris were positive for the same antigens except for tPA, Glut-1, and Tie-2, which were notably absent. Moreover, in these sprouts VEGFR-2 and VEGFR-3 expression was very high in endothelial cells, whereas many pericytes were present that were positive for PDGFR-beta, VEGFR-1, and NG2 proteoglycan and negative for alpha-SMA. In conclusion, proteins that play a role in angiogenesis are upregulated in both pre-existing and newly formed iris vasculature after treatment with VEGF-A. VEGF-A induces hypertrophy and loss of barrier function in pre-existing vessels, and induces angiogenic sprouting, characterized by marked expression of VEGFR-3 and lack of expression of tPA and Tie-2 in endothelial cells, and lack of alpha-SMA in pericytes. Our in vivo study indicates a role for alpha-SMA-negative pericytes in early stages of angiogenesis. Therefore, our findings shed new light on the temporal and spatial role of several proteins in the angiogenic cascade in vivo.
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PMID:In vivo angiogenic phenotype of endothelial cells and pericytes induced by vascular endothelial growth factor-A. 1468 16

We investigated whether stem cells (MDSC) from primary cultures of rat skeletal muscle can differentiate into the smooth muscle lineage in response to vascular endothelial growth factor (VEGF) and coculture with bladder smooth muscle cells. The MDSC were isolated from gastrocnemius muscle biopsies of normal 3-6 week-old Sprague-Dawley rats and purified by the preplate technique. Cells that took approximately 6 days to adhere to the collagen-coated flasks were termed late preplate (LP) cells, and were used in all the experiments. The early plate (EP) cells (pp1-pp4) contained some myogenic cells but were mostly fibroblasts (< 15% desmin+ cells) whereas the LP cells (pp5-pp6) were highly purified muscle-derived cells (pp6) (> 90% desmin+ cells). The muscle-derived stem cells (LP cells) were CD34+ or Sca-1+, CD45- and desmin+ by immunohistochemical staining. After two days of co-culture with bladder smooth muscle cells, about 25% of the muscle-derived stem cells were positive for alpha-smooth muscle actin (alpha-SMA)+. RT-PCR for alpha-SMA was positive in the VEGF stimulated MDSC, but negative in the absence of VEGF. In conclusion, rat muscle-derived stem cells exhibited stem cell properties (CD34+ or Sca-1+), and were not of hematogeous (CD45-) but of myogenic origin (desmin+). RT-PCR of alpha-SMA was positive in the VEGF stimulated muscle-derived stem cells.
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PMID:Isolation of muscle derived stem cells from rat and its smooth muscle differentiation [corrected]. 1505 28

Exogenous administration of transforming growth factor-beta (TGF-beta) improves wound healing by affecting cellular and molecular events involved in tissue repair. But mice with a deficiency of a key TGF-beta signaling intermediate, Smad3, paradoxically showed accelerated cutanenous wound healing, suggesting that endogenous Smad3 had inhibitory effect on cutaneous wound healing. Here we investigated the effect of exogenous expression of Smad3 in dermal fibroblasts on cutaneous wound healing. Subcutaneous injection of adenovirus-containing Smad3 complementary DNA (AdCMV-Smad3) targeting mainly dermal fibroblasts accelerated tissue repair following full-thickness dermal round wounds in rabbit ear as judged by the size of granulation tissue area, number of capillaries, and re-epithelialization rate of the wounds. Expressions of alpha-smooth muscle actin (alpha-SMA), vascular endothelial growth factor (VEGF), and fibroblast growth factor receptor were upregulated in the wounded area injected with AdCMV-Smad3. Consistent with the in vivo findings, overexpression of Smad3 induced alpha-SMA, VEGF, and TGF-beta1 expression and augmented chemotactic response in cultured dermal fibroblasts. Therefore, exogenous administration of Smad3 targeting dermal fibroblasts accelerated tissue repair in a rabbit dermal ulcer model by affecting fibroblast responses associated with wound healing. The results suggest that Smad3, when overexpressed in dermal fibroblasts, can promote wound healing.
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PMID:Exogenous Smad3 accelerates wound healing in a rabbit dermal ulcer model. 1519 65

Human fetal cord blood contains subsets of mononuclear cells with the potential to form both hematological and endothelial cells. Vascular progenitor cells, which can produce all three elements of mature blood vessels, including smooth muscle, have been identified in animals. We hypothesized that similar multipotential progenitor cells exist in humans and used the expression of alpha-smooth muscle actin (alpha-SMA) to identify such cells in fetal cord blood. Mononuclear cell preparations were isolated from human umbilical cord blood and CD34(+) and CD133(+) cells obtained by magnetic bead separation. Isolated cells were cultured on fibronectin-coated dishes with medium containing vascular endothelial growth factor, basic fibroblast growth factor, and insulin-like growth factor. mRNA was extracted, and the expression of alpha-SMA and a number of endothelial cell markers (VEGFR-2, vWF, eNOS, VE-Cadhein, PECAM-1 and Tie-2) was determined by reverse transcriptase-PCR techniques. Human umbilical vein endothelial cells (HUVECs) were used as positive controls. Freshly isolated CD34(+) and CD133(+) cells expressed all endothelial cell markers, but did not express alpha-SMA. HUVECs expressed alpha-SMA. Following 4 weeks of culture, CD34(+) isolates produced morphologically endothelial-like cells that expressed both endothelial cell markers and alpha-SMA. CD133(+) cells failed to produce morphological endothelial-like cells but expressed a range of endothelial markers. However, they did not express alpha-SMA. Following culture in an endothelial cell-promoting environment, CD34(+), but not CD133(+), isolates produced endothelial-like cells that expressed alpha-SMA. Human fetal cord blood contains a population of cells that may differentiate toward both an endothelial and a smooth muscle phenotype in culture.
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PMID:Smooth muscle alpha-actin expression in endothelial cells derived from CD34+ human cord blood cells. 1558 9

The initial phase of wound repair involves inflammation, induction of tissue factor (TF), formation of a fibrin matrix, and growth of new smooth muscle actin (alpha-SMA)-positive vessels. In diabetes, TF induction in response to cutaneous wounding, which ordinarily precedes increased expression of vascular endothelial growth factor (VEGF) and alpha-SMA transcription, is diminished, though not to a degree causing excessive local bleeding. Enhanced TF expression in wounds of diabetic mice caused by somatic TF gene transfer increased VEGF transcription and translation and, subsequently, enhanced formation of new blood vessels and elevated blood flow. Furthermore, increased levels of TF in wounds of diabetic mice enhanced wound healing; the time to achieve 50% wound closure was reduced from 5.5 days in untreated diabetic mice to 4.1 days in animals undergoing TF gene transfer (this was not statistically different from wound closure in nondiabetic mice). Thus, cutaneous wounds in diabetic mice display a relative deficiency of TF compared with nondiabetic controls, and this contributes to delayed wound repair. These data establish TF expression as an important link between the early inflammatory response to cutaneous wounding and reparative processes.
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PMID:Tissue factor as a link between wounding and tissue repair. 1598 16

Angiogenesis is essential for tumor growth, invasion, and metastatic spread. Whereas microvessel density (MVD) has been widely used as a measure of tumor-associated angiogenesis, we now wanted to examine the significance of other angiogenic markers, especially vascular proliferation (by Ki-67/factor VIII staining) and the degree of pericyte coverage [by alpha-smooth muscle actin (alpha-SMA)/factor VIII staining], in a large and population-based series of endometrial carcinoma with complete follow-up. Due to limited information on the role of lymphangiogenesis in these tumors, lymphatic vessel density (LVD) by LYVE-1 staining was also determined, as well as selected angiogenic factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D and basic fibroblast growth factor (bFGF)], which could possibly be related to vascular proliferation and lymphangiogenesis. The information on angiogenic phenotype was related to clinicopathologic features and disease progress. Median vascular proliferation, as estimated by vascular proliferation index (VPI), was 3.9% and high VPI was associated with features of aggressive tumors and decreased survival. The prognostic effect of VPI was superior to that of MVD. Presence of pericyte coverage, as estimated by the alpha-SMA index (SMAI), was 35% and low SMAI was significantly associated with vascular invasion by tumor cells and impaired prognosis. Peritumoral lymphatic vessels (LVD-pt) were found in 39.5% of the cases and high LVD-pt was significantly associated with aggressive tumor features and decreased survival. In multivariate survival analysis, only the extent of vascular proliferation had independent prognostic effect, in addition to well-known clinicopathologic factors, whereas MVD did not have significant prognostic value. In conclusion, our study indicates that vascular proliferation is a meaningful variable in assessing the angiogenic phenotype of endometrial carcinoma.
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PMID:Vascular proliferation is important for clinical progress of endometrial cancer. 1654 Jun 84

Paraquat (PQ)-induced pulmonary toxicity is characterized by initial development of pulmonary edema, infiltration of inflammatory cells, and damage to the alveolar epithelium, which may progress to severe fibrosis. However, the exact role of PQ in the progression of the pathogenesis has not been clearly established. To understand the mechanism of PQ in pulmonary toxicity, we developed an animal model of PQ-induced lung injury by intranasal instillation of PQ solution using C57Black/6J mice. Twenty microliters of PQ solution (0.01, 0.01, and 0.04 mg/mouse) was applied through the nares, and the same amount of vehicle was applied in control mice. The pathological progression of lung pathology in our mouse model was very similar to that of patients suffering from PQ poisoning. The lungs of some animals exposed to PQ showed acute fulmination, resulting in death from 5 days post-exposure, but others showed a more protracted injury, resulting in typical pulmonary fibrosis at 3 weeks. Using this PQ-poisoned mouse model, we examined the gene expression at the initial destructive phase (within 5 days) that fibrosis has not completely developed. We prepared RNAs after 6h, 24h, and 5 days and examined the changes of the expression levels for 45 selected genes. The genes showing >2-fold increase at 6h or a time-dependent decrease during this experimental period may be the early markers for the destructive phase. These genes are Mt1, Mt2, Hmox1, Gcl, GR, IL-6, IL-13, Txn1, Fas, FasL, Lpin2, Mmp1a, Mmp12, Sfp-B, Sfp-D, CAT, EC-SOD, GST, and Pltp. On the other hand, the genes involved in the development of fibrosis, such as procollagen, Fn1, Eln, SMA, and Mmp9, Timp1 were significantly increased on day 5, not at 6h nor at 24h, after PQ treatment (the late marker). The genes showing a significant increase (Mmp3 and Mmp8) or decrease (VEGFA) at 24h and 5 days and not at 6h may be also the late markers. These changes in gene expression, which are equalled to functional activities of proteins, will be the targets for future studies focused on the development on PQ-induced pulmonary damage.
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PMID:Mouse model of paraquat-poisoned lungs and its gene expression profile. 1721 68

Tetrandrine (Tet) (C38H42O8N2; molecular weight, 622), an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to elicit anti-inflammatory and anti-fibrotic effects in pulmonary diseases, but the mechanism of action has yet to be investigated. In this study, we tested whether Tet exerts anti-fibrotic effects on rat hepatic fibrosis through anti-NFkappaB pathways. After bile-duct ligation, rats were given Tet (1 or 5 mg/kg) or silymarin (50 mg/kg, as a positive control) by gavage twice daily for 3 weeks. Liver sections were taken for Sirius red quantitative scoring, immunofluorescence double staining of alpha-smooth muscle actin (alpha-SMA) and NFkappaB, and for quantitative determinations of the mRNA expression levels of TGF-beta1, alpha-SMA, collagen 1alpha2, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), metallothionein, vascular endothelial growth factor (VEGF), and VEGF type II receptor (VEGFR2) genes. The results showed that both Tet and silymarin treatment significantly reduced the fibrosis scores and hepatic collagen content of BDL rats, compared with no treatment. Both Tet and silymarin treatments decreased the number of alpha-SMA- and NFkappaB-positive cells in fibrotic livers. Moreover, Tet and silymarin treatments attenuated the mRNA expression levels of TGF-beta1,alpha-SMA, collagen 1alpha2, iNOS, ICAM-1, VEGF, and VEGFR2 genes, and induced the mRNA expression of the metallothionein gene. This study suggests that the anti-fibrotic effects of Tet were related to the reduction of fibrosis-related gene transcription, the attenuation of NFkappaB-activated pathways, and the induction of metallothionein gene transcription in the livers of BDL rats.
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PMID:Anti-fibrotic effects of tetrandrine on bile-duct ligated rats. 1721 62


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