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 examined the biopsy specimens of 62 patients with diabetic nephropathy to establish whether the myofibroblast (MF) has a role in progressive interstitial fibrosis and to ascertain whether a relationship existed between MF activity and severity of arteriolosclerosis. MF were identified by morphology and alpha smooth muscle actin (alpha SMA) immunostaining. Analysis of vascular injury was performed by counting the number of interstitial arterioles after staining endothelial cells with von Willebrand factor (VWF) antibody. Arteriosclerosis was quantified by using a computer-aided image analyzer to measure the arteriolar wall surface and total arteriolar surface area, and the ratio of wall to total surface area was expressed as the index of arteriosclerosis (IA). Fractional area of interstitium (IFA), alpha SMA, and collagen III (Coll III) were quantitated by point counting. Results were related to structural and functional parameters using rank correlation coefficients. There was a strong correlation between IFA and Coll III staining (r = 0.83; P < 0.001). The alpha SMA staining correlated with IFA (r = 0.56; P < 0.001) and Coll III (r = 0.47; P < 0.001), and there were significant correlations between alpha SMA and total urinary protein (r = 0.47; P < 0.001), renal function (plasma creatinine) at time of biopsy (r = 0.51; P < 0.001), and the percent change in plasma creatinine after 4 years (delta Cr) (r = 0.37; P = 0.01). The IA correlated significantly with Coll III (r = 0.29; P = 0.02), glomerular filtration rate (GFR) (r = 0.39; P = 0.008), and creatinine (r = 0.33; P = 0.01), but no correlation was observed between alpha SMA and IA (r = 0.16; P = 0.23) or IA and delta Cr (r = -0.04; P = 0.6). Strong correlations could be shown between arteriolar density, IFA (r = 0.75; P < 0.001), alpha SMA (r = -0.36; P = 0.034), and Coll III (r = -0.66; P < 0.0001). The MF appears to have a significant role in the progression of diabetic nephropathy. Ischemia secondary to arteriosclerosis may contribute to interstitial fibrosis through fibroblast modulation into MF.
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PMID:Myofibroblasts and arteriolar sclerosis in human diabetic nephropathy. 918 78

The present study was undertaken to examine the cellular composition of the aortic wall in Takayasu's arteritis and to investigate the association of different cell types in the immuno-inflammatory reactions of this disease. Specimens of aortic wall affected by Takayasu's arteritis were obtained from 10 patients (five male, five female), aged 32 to 68 years (mean 49.5 years) at elective operation. The mean duration of disease was 6.5 years (range 2 months to 13 years). Specimens were embedded in paraffin and the sections stained with antibodies to CD3 (to identify T cells), CD20 (B cells), S-100 (dendritic cells), CD15 (granulocytes), CD68 (macrophages), alpha-SMA (smooth muscle cells) and von Willebrand factor (endothelial cells). Immunohistochemical examination demonstrated that all specimens showed histological alteration with the replacement of the muscular and elastic layers of the media and adventitia by dense fibrous tissue, and were characterized by varying degrees of inflammatory cell infiltration. In five cases, inflammatory nodules consisting of numerous T cells and B cells were observed in the adventitia. Within the inflammatory nodules, as well as around areas of neovascularization in the deep portion of the intima, lymphocytes were co-localized with dendritic cells. In addition, in the adventitia, the accumulation of a large number of granulocytes was observed. The present study demonstrates that immune inflammation is a typical feature of Takayasu's disease, and that the interactions between dendritic cells and lymphocytes may be important in the control of the immune reactions in this vascular pathology.
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PMID:Immunophenotypic analysis of the aortic wall in Takayasu's arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions. 1073 51

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

Smooth muscle cells (SMCs) under shear stress may alter their gene expression patterns to adapt to a new hemodynamic environment. Their plasticity may play an important role in vascular development, healing, and remodeling as well as vascular lesion formation under abnormal environmental conditions. A mouse vascular SMC line (P53LMACO1) cultured under shear stress significantly increased the mRNA levels of endothelial cell markers including Platelet-endothelial cell adhesion molecule-1 (PECAM-1), von Willebrand factor (vWF), and VE-cadherin, while significantly decreasing the mRNA levels of SMC markers including alpha-smooth muscle actin (alpha-SMA), calponin-1, smooth muscle myosin heavy chain (SMMHC), and transgelin as compared to static control cells. Protein levels of PECAM-1 and vWF were significantly increased, while protein levels of alpha-SMA were substantially decreased in the shear stress-cultured cells. In addition, shear stress-cultured cells showed an enhanced capability to form capillary-like structures on Matrigel. Thus, shear stress may promote endothelial cell transdifferentiation from SMCs.
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PMID:Shear stress induces endothelial transdifferentiation from mouse smooth muscle cells. 1679 21

Recent evidence suggests that bone marrow (BM)-derived cells may integrate into the kidney, giving rise to functional renal cell types, including endothelial and epithelial cells and myofibroblasts. BM-derived cells can contribute to repair of the renal peritubular capillary (PTC) network following acute ischemic injury. However, the cell fate and regulation of BM-derived cells during the progression of chronic renal disease remains unclear. Using chimeric mice transplanted with enhanced green fluorescent protein (EGFP)-expressing BM, we demonstrate that the number of BM-derived myofibroblasts coincided with the development of fibrosis in a mouse adriamycin (ADR)-induced nephrosis model of chronic, progressive renal fibrosis. Four weeks after ADR injection, increased numbers of BM-derived myofibroblasts were observed in the interstitium of ADR-injected mice. Six weeks after ADR injection, more than 30% of renal alpha-smooth muscle actin (+) (alpha-SMA+) interstitial myofibroblasts were derived from the BM. In addition, BM-derived cells were observed to express the endothelial cell marker CD31 and the myofibroblast marker alpha-SMA. Blockade of p38 mitogen-activated protein kinase (MAPK) and transforming growth factor (TGF)-beta1/Smad2 signaling was found to protect BM-derived PTC endothelial cells and inhibit the number of BM-derived von Willebrand factor (vWF)(+)/EGFP(+)/alpha-SMA(+) cells, EGFP(+)/alpha-SMA(+) cells, and total alpha-SMA(+) cells in ADR-injected mice. Inhibition of the p38 MAPK and TGF-beta1/Smad signaling pathways enhanced PTC repair by decreasing endothelial-myofibroblast transformation, leading to structural and functional renal recovery and the attenuation of renal interstitial fibrosis. Investigation of the signaling pathways that regulate the differentiation and survival of BM-derived cells in a progressive disease setting is vital for the successful development of cell-based therapies for renal repair.
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PMID:The contribution of bone marrow-derived cells to the development of renal interstitial fibrosis. 1717 67

The objective of this study was to determine whether cyclic strain could promote human umbilical vein endothelial cells (HUVECs) to express markers in common with the mature smooth muscle cell (SMC) phenotype, suggesting endothelial cell to SMC transdifferentiation. HUVECs were cultured on stretched membranes at 10% stretch and 60 cycles/min for 24-96 hr, and demonstrated elongation with enhanced and organized F-actin distribution. By using real-time polymerase chain reaction analysis, the mRNA levels of five specific SMC markers, SM22-alpha, alpha-smooth muscle actin (alpha-SMA), caldesmon-1, smooth muscle myosin heavy chain (SMMHC), and calponin-1 were significantly increased in cyclic strain-treated HUVECs as compared with those in static control cells. Protein levels of SM22-alpha and alpha-SMA were also substantially increased by Western blot and immunofluorescence staining. In addition, two specific endothelial markers, von Willebrand factor (vWF) and vascular endothelial growth factor receptor-2 (VEGFR-2), showed a reduction in mRNA expression. In addition, cyclic strain-induced increase of SM22-alpha and alpha-SMA expression were reversible when cells were cultured back to the static condition. These results demonstrate a possible endothelial cell to SMC transdifferentiation in response to cyclic strain. Hemodynamic forces in modulating endothelial phenotype may play an important role in the vascular system.
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PMID:Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells. 1717 52

The status of angiogenic switching was examined in alveolar capillaries of primary lung adenocarcinoma (ADC) from 10 patients and primary squamous cell carcinoma (SCC) from 11 patients, using immunostaining for CD31, thrombomodulin, von Willebrand factor (vWF), collagen types IV and VII, and alpha-smooth muscle actin (alpha-SMA). We applied the TdT-mediated dUTP nick-end labeling assay and the reverse transcription-polymerase chain reaction for vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). In bronchioloalveolar and papillary subtypes of ADC, the neoplastic cells, replacing the normal alveolar epithelial cells, had spread over alveolar walls and adhered firmly to alveolar interstitium as shown by the development of type IV collagen. Neoplastic cells of SCC were characterized by local proliferation in alveolar sacs without firm attachment to alveolar walls. Tumor lesions of SCC had often developed necrotic foci of various size. In ADC and SCC, alveolar capillary endothelial cells newly obtained reactivity to vWF. Such segments of endothelial cells lost surface thrombomodulin expression. CD31 was consistently expressed in normal and ADC tissues, but each endothelial cell marker was often attenuated or even lost in SCC, suggesting degeneration or necrosis of the alveolar capillaries. The capillary pericytes and interstitial fibroblasts were often hypertrophic and developed alpha-SMA in the cytoplasm in ADC, but they became atrophic in SCC. In ADC, apoptosis occurred in cells of alveolar capillaries more frequently in the peripheral zone than in the deeper zone of the tumor, whereas the frequency was not consistent in SCC. In microdissected alveolar wall tissues, mRNA expression patterns of VEGF isoforms and VEGFRs were similar in both ADC and SCC. In ADC, de novo angiogenic switching took place in cytoplasm as a unit of cells segments in alveolar capillary endothelium. Suppression of angiogenic switching in SCC implies that factors other than VEGF-VEGFR interaction, such as physical contact and compression of tumor cells, might play a critical role in alveolar capillaries.
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PMID:Angiogenic switching in the alveolar capillaries in primary lung adenocarcinoma and squamous cell carcinoma. 1796 28

Cells were isolated from four human amniotic membranes, and their biological characteristics analyzed during ex vivo expansion. Morphologically homogenous populations of fibroblast-like cells were obtained from the second or third passage. Under the appropriate culture conditions, these human amniotic membrane-derived mesenchymal cells (HAM) were shown to differentiate into adipocytes, osteocytes, chondrocytes and neuronal cells, as visualized by Oil Red O, von Kossa, alcian blue, anti-Neu N, and anti-Gal C antibody staining, respectively. Immunophenotype analysis of HAM cells revealed the presence of antigens for SSEA-3, SSEA-4, collagen type-I, -II, -III, -IV, -XII, fibronectin, alpha-SMA, vimentin, desmin, cytokeratin18 (CK18), HCAM-1, fibroblast surface protein, and human leukocyte antigen (HLA) ABC. ICAM-1 protein was weakly detectable, and proteins of TRA-1-60, VCAM-1, von Willebrand factor, PECAM-1, and HLA DR were not detected. HAM cells reached senescence after 14.5+/-0.9 passages, over a period of 146.8+/-8.9 days, and underwent an average of 36.9 4.7 population doublings. RT-PCR analysis showed that all four HAM cell lines consistently expressed genes of Oct-4, Rex-1, SCF, NCAM, nestin, BMP-4, GATA-4, HNF-4alpha, vimentin, and CK18, regardless of the passage number. The genes of Brachyury, FGF-5, Pax-6, and BMP2 were never expressed. Strikingly, alpha-fetoprotein (alphaFP), HLA ABC, and HLA DR genes were expressed in an earlier passage but not expressed in later passages. Telomerase activity of two HAM lines was discernable upon the third passage. These observations strongly suggest that HAM might be immune-privileged and, thus, advantageous as therapeutic cells.
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PMID:Ex vivo characteristics of human amniotic membrane-derived stem cells. 1815 18

Current scientific attempts to generate in vitro tissue-engineered living blood vessels (TEBVs) show substantial limitations, thereby preventing routine clinical use. In the present report, we describe a novel biotechnology concept to create living small diameter TEBV based exclusively on microtissue self-assembly (living cellular re-aggregates). A novel bioreactor was designed to assemble microtissues in a vascular shape and apply pulsatile flow and circumferential mechanical stimulation. Microtissues composed of human artery-derived fibroblasts (HAFs) and endothelial cells (HUVECs) were accumulated and cultured for 7 and 14 days under pulsatile flow/mechanical stimulation or static culture conditions with a diameter of 3mm and a wall thickness of 1mm. The resulting vessels were analyzed by immunohistochemistry for extracellular matrix (ECM) and cell phenotype (von Willebrand factor, alpha-SMA, Ki67, VEGF). Self-assembled microtissues composed of fibroblasts displayed significantly accelerated ECM formation compared to monolayer cell sheets. Accumulation of vessel-like tissue occurred within 14 days under both, static and flow/mechanical stimulation conditions. A layered tissue formation was observed only in the dynamic group, as indicated by luminal aligned alpha-SMA positive fibroblasts. We could demonstrate that self-assembled cell-based microtissues can be used to generate small diameter TEBV. The significant enhancement of ECM expression and maturation, together with the pre-vascularization capacity makes this approach highly attractive in terms of generating functional small diameter TEBV devoid of any foreign material.
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PMID:A novel concept for scaffold-free vessel tissue engineering: self-assembly of microtissue building blocks. 2022 67


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