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Alpha-smooth Muscle Actin (alpha-smooth + muscle_actin)
Selected AbstractsmTOR as a potential therapeutic target for treatment of keloids and excessive scarsEXPERIMENTAL DERMATOLOGY, Issue 5 2007C. T. Ong Abstract:, Keloid is a dermal fibroproliferative disorder characterized by excessive deposition of extracellular matrix (ECM) components such as collagen, glycoproteins and fibronectin. The mammalian target of rapamycin (mTOR) is a serine/theronine kinase which plays an important role in the regulation of metabolic processes and translation rates. Published reports have shown mTOR as regulator of collagen expression and its inhibition induces a decrease in ECM deposition. Our aim was to investigate the role of mTOR in keloid pathogenesis and investigate the effect of rapamycin on proliferating cell nuclear antigen (PCNA), cyclin D1, collagen, fibronectin and alpha-smooth muscle actin (, -SMA) expression in normal fibroblasts (NF) and keloid fibroblasts (KF). Tissue extracts obtained from keloid scar demonstrated elevated expression of mTOR, p70KDa S6 kinase (p70S6K) and their activated forms, suggesting an activated state in keloid scars. Serum stimulation highlighted the heightened responsiveness of KF to mitogens and the importance of mTOR and p70S6K during early phase of wound healing. Application of rapamycin to monoculture NF and KF, dose- and time-dependently downregulates the expression of cytoplasmic PCNA, cyclin D1, fibronectin, collagen and , -SMA, demonstrating the anti-proliferative effect and therapeutic potential of rapamycin in the treatment of keloid scars. The inhibitory effect of rapamycin was found to be reversible following recovery in the expression of proteins following the removal of rapamycin from the culture media. These results demonstrate the important role of mTOR in the regulation of cell cycle and the expression of ECM proteins: fibronectin, collagen and , -SMA. [source] Activation of hepatic stellate cells after phagocytosis of lymphocytes: A novel pathway of fibrogenesis,HEPATOLOGY, Issue 3 2008Nidal Muhanna Increased CD8-T lymphocytes and reduced natural killer (NK) cells contribute to hepatic fibrosis. We have characterized pathways regulating the interactions of human hepatic stellate cells (HSCs) with specific lymphocyte subsets in vivo and in vitro. Fluorescence-activated cell sorting (FACS) was used to characterize human peripheral blood lymphocytes (PBLs) and intrahepatic lymphocytes (IHLs) obtained from healthy controls and from patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) with advanced fibrosis. Liver sections were analyzed by immunohistochemistry and confocal microscopy. To investigate in vitro interactions, PBLs from healthy controls or patients with HCV cirrhosis were co-cultured with an immortalized human HSC line (LX2 cells) or with primary HSCs. Significant alterations in lymphocyte distribution were identified in IHLs but not PBLs. The hepatic CD4/CD8 ratio and NK cells were significantly reduced in HBV/HCV patients. Expression of alpha-smooth muscle actin and infiltration of CD4, CD8, and NK cells were readily apparent in liver sections from patients with cirrhosis but not in healthy controls. Lymphocytes from each subset were in proximity to HSCs primarily within the periportal regions, and some were directly attached or engulfed. In culture, HSC activation was stimulated by HCV-derived CD8-subsets but attenuated by NK cells. Confocal microscopy identified lymphocyte phagocytosis within HSCs that was completely prevented by blocking intracellular adhesion molecule 1 (ICAM-1) and integrin molecules, or by irradiation of HSCs. LX2 knockdown of either Cdc42 or Rac1 [members of the Rho-guanosine triphosphatase (GTPase) family] prevented both phagocytosis and the activation of HSC by HCV-derived lymphocytes. Conclusion: The CD4/CD8 ratio and NK cells are significantly decreased in livers with advanced human fibrosis. Moreover, disease-associated but not healthy lymphocytes are engulfed by cultured HSCs, which is mediated by the Rac1 and Cdc42 pathways. Ingestion of lymphocytes by HSCs in hepatic fibrosis is a novel and potentially important pathway regulating the impact of lymphocytes on the course of hepatic fibrosis. (HEPATOLOGY 2008.) [source] The role of angiogenesis, vascular maturation, regression and stroma infiltration in dormancy and growth of implanted MLS ovarian carcinoma spheroidsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Assaf Gilead Abstract MLS ovarian epithelial carcinoma multicellular spheroids xenografted subcutaneously in CD-1 nude mice displayed growth delay, or dormancy, of up to 52 days. In the study reported here, implanted MLS spheroids were used for testing the role of angiogenesis and vascular maturation in triggering the initiation of tumor progression. The kinetics and impact of neovascular maturation and functionality, in dormancy, and growth of MLS spheroid xenografts were studied noninvasively by BOLD contrast MRI. MR data were supported by histologic staining for biotinylated albumin as a blood pool marker and alpha-smooth muscle actin (alpha-SMA) as marker for perivascular mural cells. Although the tumor periphery showed higher levels of total and mature vasculature than normal skin, the fraction of mature out of the total vessels as detected by MRI vascular maturation index (VMIMRI) was significantly lower in the tumor both before and after tumor exit from dormancy. The neovasculature induced by the implanted spheroid was unstable and showed cycles of vessel growth and regression. Surprisingly, this instability was not restricted to the immature vessels, but rather included also regression of mature vessels. During dormancy, neovasculature was predominantly peripheral with no infiltration into the implanted spheroid. Infiltration of alpha-SMA positive stroma cells into the spheroid was associated with functional vascularization and tumor growth. Thus, stroma infiltration and vascular maturation are an important checkpoint linking the angiogenic switch with initiation of tumor progression. © 2003 Wiley-Liss, Inc. [source] Myopericytoma: report of two cases associated with traumaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2008Alvaro C. Laga Myopericytoma is a rare, recently described tumor demonstrating a hemangiopericytoma-like vascular pattern. We present two cases of myopericytoma associated with trauma: a 64-year-old man who developed several nodules on his nose four months after sustaining multiple abrasions to his forehead and nose, and a 72-year-old woman with a solitary growth in the alveolar ridge of unknown duration. Biopsy specimens of the lesions in both cases demonstrated a striking concentric perivascular proliferation of bland spindle-shaped pericytic cells characteristic of myopericytoma. Despite sharing morphologic features with angioleiomyoma, myofibroma and glomus tumor, myopericytoma is thought to represent a distinct perivascular myoid neoplasm of skin and soft tissues. The tumor is characterized by a radial and perivascular arrangement of ovoid, spindled to round neoplastic cells that are immunoreactive to alpha-smooth muscle actin, often for h-caldesmon as well as smooth muscle myosin-heavy chain, and usually negative for desmin antibodies. Most cases of myopericytoma are benign, however, local recurrence and malignancy have recently been reported, Myopericytoma can be multifocal involving a single or multiple anatomic regions, and tends to occur in dermal and superficial soft tissues of adults primarily on the extremities. Our cases are unusual examples of myopericytoma manifesting as multiple nodules on the nose, and a solitary growth on the buccal mucosa after trauma. [source] Inhibition of plasminogen activator inhibitor-1 expression by siRNA in rat hepatic stellate cellsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2008Ping-Fang Hu Abstract Background and Aim:, The plasminogen activator/plasmin system is known to regulate the extracellular matrix turnover. The aim of this study was to detect the role of plasminogen activator inhibitor-1 (PAI-1) during liver fibrogenesis and investigate the functional effects of PAI-1 gene silencing in rat hepatic stellate cells (HSCs) using small interfering RNA (siRNA). Methods:, Hepatic fibrosis in rats was induced through serial subcutaneously injections of CCl4 and the expression of PAI-1 was detected by immunohistochemistry and reverse transcription,polymerase chain reaction (PCR). PAI-1 siRNA molecules were constructed and transiently transfected into HSC-T6 using the cell suspension transfection method. The pSUPER RNA interfering system was used to establish the HSC stable cell line pSUPER-shPAI. Expression of alpha-smooth muscle actin, transforming growth factor-beta, tissue inhibitor of metalloproteinases-1, and collagen types I and III were evaluated by real-time PCR. Cell proliferation and the cell cycle were determined by the methyl thiazolyl tetrazolium (MTT) method and flow cytometry. Collagen content in HSCs supernatant was evaluated by enzyme-linked immunosorbent assay. Results:, The results showed that PAI-1 was upregulated during liver fibrosis, and its expression was closely correlated with the deposition of collagens. SiRNA molecules were successfully transfected into HSCs and induced inhibition of PAI-1 expression time dependently. Moreover, PAI-1 siRNA treatment downregulated alpha-smooth muscle actin, transforming growth factor-beta, tissue inhibitor of metalloproteinases-1 expression, and inhibited collagen types I and III synthesis both at the mRNA and protein level in transiently and stably transfected HSCs. Conclusions:, This study suggests a significant functional role for PAI-1 in the development of liver fibrosis and that downregulating PAI-1 expression might present as a potential strategy to treat liver fibrosis. [source] The role of the fibrocyte in intimal hyperplasiaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2006R. L. VARCOE Summary.,Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow-derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha-smooth muscle actin (, -SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and , -SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and , -SMA) and also to double stain for CD34 and , -SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury. [source] Can hepatic stellate cells express alpha-smooth muscle actin in normal human liver?LIVER INTERNATIONAL, Issue 4 2001Sébastien Lepreux [source] Upregulation of immunoreactivity of endothelin-1 and ,-SMA in PDL microvasculature following acute tooth loading: an immunohistochemical study in the marmosetORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 2 2003MR Sims Structured Abstract Authors , Sims MR, Ashworth JF, Sampson WJ Objectives , To test the hypothesis that a continuous mechanical tooth load would elevate immunoreactivity of endothelin-1 (ET-1) and alpha-smooth muscle actin (,-SMA) in the periodontal ligament (PDL) microvasculature. Design , A randomized control study employing 1.5 h of loading to first molars. Setting and Sample Population , Orthodontic Research Laboratory, Dental School, Adelaide University. Four young adult, male marmoset monkeys were consecutively anaesthetized and treated. Experimental Variable , An external telescoping frame applied a jaw closing load (120,200 g) transmitted occlusally, via a rubber pad, to randomly assigned mandibular left or right first molars. Contralateral molars were used as controls. Outcome Measure , Undemineralized, midsagittal, mandibular molar slices, ,150 ,m thick were immunolabelled with ET-1 and ,-SMA antibodies and examined in a confocal laser scanning microscope (CLSM) for vascular endothelium and smooth muscle immunolabelling. Results , Three categories of post-capillary-sized venule endothelial cell immunolabelling occurred: endothelium labelled solely with ET-1; endothelium labelled solely with ,-SMA; endothelium labelled with both ET-1 and ,-SMA. In endothelial cells, the ,-SMA showed a moderate cytoplasmic distribution with dense peripheral concentration. Loading increased arteriole ,-SMA actin labelling. Conclusion , Scattered expression of ET-1 is the default state in primate PDL endothelial cells. Increased antigenicity of endothelial cells to both ET-1 and ,-SMA, and of arteriolar smooth muscle to ,-SMA, is a response to shear and compression loads. [source] Lobular capillary hemangioma of the oral mucosa: Clinicopathological study of 43 cases with a special reference to immunohistochemical characterization of the vascular elementsPATHOLOGY INTERNATIONAL, Issue 1 2003Makoto Toida Clinical and histopathological features were investigated in 43 cases of oral lobular capillary hemangiomas (LCH) with a special reference to characteristics of the vascular elements. The lesions affected females more than males by a ratio of 1:1.5. Average age of the patients was 52.7 years. The lesions involved the gingiva (n = 15), the tongue (n = 13), the labial mucosa (n = 10) and other sites. The lesions appeared usually as a pedunculated mass with ulceration; size of the lesions was up to 15 mm. Histologically, a lobular area and an ulcerative area were distinguished. The density of vessels was about 1045/mm2 and 160/mm2 in the lobular and ulcerative areas, respectively. The average diameter of the vascular lumen was 9.1 5.6 mm (range: 2.8,42.0 mm) and 18.8 20.9 mm (range: 5.6,139.7 mm) in the lobular and ulcerative areas, respectively. In the lobular area, most of the vessels had an inner layer of endothelial cells showing positive reaction for von Willebrand factor (vWF) and CD34, as well as an outer layer of mesenchymal cells showing positive reaction for alpha-smooth muscle actin (ASMA). However, in the ulcerative area, there was a variety of types of vessels consisting of various proportions of both endothelial and ASMA-positive perivascular mesenchymal cells. These results indicate that most of the vascular elements in the lobular area resemble more pericapillary microvascular segments than they do capillaries. Thus, the authors propose the term ,lobular pericapillary hemangioma' to represent this type of lesion. [source] Congenital leiomyomatous epulis: A case report with immunohistochemical studyPATHOLOGY INTERNATIONAL, Issue 12 2000Yasunori Takeda The histologic and immunohistochemical findings of an extremely rare case of congenital soft tissue mass on the alveolar ridge in an infant are reported. The lesion clinically mimicked an ordinary congenital epulis (congenital granular cell epulis, granular cell tumor of the newborn); however, histologically it consisted of a conglomerate of spindle-shaped cells, akin to smooth muscle cells, which formed interlacing and whorled fasciculi. Nerve fibers with myxoid degeneration, capillaries and muscle walled small vessels intermingled with fasciculi of spindle-shaped cells. The border between the conglomerate of spindle-shaped cells and the surrounding connective tissue was not evident. Immunohistochemically, most of the spindle-shaped cells were intensely positive for antibodies to alpha-smooth muscle actin, HHF-35 and desmin. These findings suggest that the lesion was composed of mature smooth muscle cells that were of hamartomatous or choristomatous nature. The term ,congenital leiomyomatous epulis' is proposed. [source] Adenomyosis with a sex cord-like stromal elementPATHOLOGY INTERNATIONAL, Issue 4 2000Masaharu Fukunaga A case of adenomyosis with a sex cord-like stromal element is described. The element was an incidental, solitary, microscopic finding in a focus of adenomyosis. It was characterized by cord and trabecular arrangements of round to polygonal shaped cells in the endometrioid stroma. The cells were immunohistochemically positive for desmin and alpha-smooth muscle actin but negative for sex cord markers (alpha-inhibin and O13). The element appears to originate from the endometrial stromal cells through smooth muscle metaplasia. [source] Pathological airway remodelling in inflammationTHE CLINICAL RESPIRATORY JOURNAL, Issue 2010Gunilla Westergren-Thorsson Abstract Introduction:, Airway remodelling refers to a wide pattern of patophysiological mechanisms involving smooth muscle cell hyperplasia, increase of activated fibroblasts and myofibroblasts with deposition of extracellular matrix. In asthma, it includes alterations of the epithelial cell layer with goblet cell hyperplasia, thickening of basement membranes, peri-bronchial and peri-broncheolar fibrosis. Moreover, airway remodelling occurs not only in asthma but also in several pulmonary disorders such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and systemic sclerosis. Asthma treatment with inhaled corticosteroids does not fully prevent airway remodelling and thus have restricted influence on the natural course of the disease. Objectives:, This review highlights the role of different fibroblast phenotypes and potential origins of these cells in airway remodelling. Results:, During inflammatory conditions, such as asthma, fibroblasts can differentiate into an active, more contractile phenotype termed myofibroblast, with expression of stress fibres and alpha-smooth muscle actin. The origin of myofibroblasts has lately been debated, and three sources have been identified: recruitment and differentiation of resident tissue fibroblasts; fibrocytes , circulating progenitor cells; and epithelial,mesenchymal transition. Conclusion:, It is clear that airway mesenchymal cells, including fibroblasts/myofibroblasts, are more dynamic in terms of differentiation and origin than has previously been recognised. Considering that these cells are key players in the remodelling process, it is of utmost importance to characterise specific markers for the various fibroblast phenotypes and to explore factors that drive the differentiation to develop future diagnostic and therapeutic tools for asthma patients. Please cite this paper as: Westergren-Thorsson G, Larsen K, Nihlberg K, Andersson-Sjöland A, Hallgren O, Marko-Varga G and Bjermer L. Pathological airway remodelling in inflammation. Clin Respir J 2010; 4 (Suppl. 1): 1,8. [source] Variable expression of tenascin-C, osteopontin and fibronectin in inflammatory myofibroblastic tumour of the lungAPMIS, Issue 2 2010RIITTA KAARTEENAHO Kaarteenaho R, Sormunen R, Pääkkö P. Variable expression of tenascin-C, osteopontin and fibronectin in inflammatory myofibroblastic tumour of the lung. APMIS 2010; 118: 91,100. The aim of this study was to analyse the expression of tenascin-C, osteopontin and fibronectin in inflammatory myofibroblastic tumour of the lung, which is a rare tumour of unknown aetiology. Nine patients with an inflammatory myofibroblastic tumour of lung were studied by immunohistochemistry for the presence of tenascin-C, osteopontin, fibronectin and alpha-smooth muscle actin, which is a common marker for myofibroblasts. The ultrastructure of myofibroblasts was confirmed by transmission electron microscopy. The expression of tenascin-C, osteopontin, fibronectin and alpha-smooth muscle actin was also studied by immunoelectron microscopy. All cases displayed all of the studied extracellular matrix proteins and also alpha-smooth muscle actin-positive spindle-shaped fibroblastic cells that were undoubtedly myofibroblasts. The immunoelectron microscopic studies demonstrated labelling for alpha-smooth muscle actin in intracellular filament bundles within myofibroblasts, for fibronectin in the extracellular filaments of the fibronexus and for tenascin-C extracellularly often adjacent to myofibroblasts. Labels for osteopontin were observed within myofibroblasts and plasma cells. These results demonstrate that tenascin-C, osteopontin and fibronectin were expressed in all three kinds of subtypes of inflammatory myofibroblastic tumours of the lung and further, variable amounts of myofibroblasts could be observed by light and transmission electron microscopy as well as by immunoelectron microscopic techniques. [source] Bridging necrosis and reticulin bridging fibrosis induced by intrahepatic involvement of acute biphenotypic leukemia,APMIS, Issue 12 2006Case report A 47-year-old Japanese woman was diagnosed as having acute biphenotypic leukemia with association of t(9;22)(q34;q11). Cholestatic liver dysfunction arose, and she died of cachexia and intracranial hemorrhage. Autopsy showed unusual hepatic fibrosis. In the liver, bridging infiltration, bridging necrosis and bridging fibrosis by leukemic cells were seen. It seemed that the degree of fibrosis was associated with the number of aggregates of infiltrating leukemic cells. The fibrotic foci were predominantly composed of reticulin and collagen fibers, and distortion of the lobules was observed. Immunohistochemically, dense bundles of alpha-smooth muscle actin (ASMA)-positive stromal cells, namely activated hepatic stellate cells (HSCs), were observed in the immature fibrotic foci as well as along the sinusoids densely infiltrated by leukemic cells. No cells positive for TGF-,1 or PDGF-BB were identified. In conclusion, extensive intrahepatic involvement by neoplastic cells in adult acute biphenotypic leukemia may cause the unusual "disorganized" hepatic fibrosis. [source] | |||||||||||||||||||