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Smoothelin,a new marker to determine the origin of liver fibrogenic cells

查看全文 作  者:Sébastien [1]Lepreux;Christelle [2,3]Guyot;Fabrice [4]Billet;Chantal [2]Combe;Charles [2]Balabaud;Paulette Bioulac-[2]Sage;Alexis [4]Desmoulière 高影响力作者 机构地区:[1]CHU Bordeaux, Hopital Pellegrin, Service d’Anatomie Pathologique, F-33076 Bordeaux, France;[2]U889 and Université Victor Segalen Bordeaux 2, F-33076 Bordeaux, France;[3]Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital Zurich, 8006 Zurich, Switzerland;[4]Facultés de Médecine et de Pharmacie, Université de Limoges, EA 6309, F-87025 Limoges,France高影响力机构 出  处:《World Journal of Gastroenterology》索引2013年第19卷第48期,共8页高影响力期刊 基  金:Supported by In part a grant from the French Ministry of Research 摘  要:AIM:To explore this hypothesis that smooth muscle cells may be capable of acquiring a myofibroblastic phenotype,we have studied the expression of smoothelin in fibrotic conditions.METHODS:Normal liver tissue(n=3)was obtained from macroscopically normal parts of hepatectomy,taken at a distance from hemangiomas.Pathological specimens included post-burn cutaneous hypertrophic scars(n=3),fibrotic liver tissue(n=5),cirrhotic tissue(viral and alcoholic hepatitis)(n=5),and hepatocellular carcinomas(n=5).Tissue samples were fixed in 10%formalin and embedded in paraffin for immunohistochemistry or were immediately frozen in liquid nitrogen-cooled isopentane for confocal microscopy analysis.Sections were stained with antibodies against smoothelin,which is expressed exclusively by smooth muscle cells,andα-smooth muscle actin,which is expressed by both smooth muscle cells and myofibroblasts.RESULTS:In hypertrophic scars,α-smooth muscle actin was detected in vascular smooth muscle cells and in numerous myofibroblasts present in and around nodules,whereas smoothelin was exclusively expressed in vascular smooth muscle cells.In the normal liver,vascular smooth muscle cells were the only cells that expressα-smooth muscle actin and smoothelin.In fibrotic areas of the liver,myofibroblasts expressingα-smooth muscle actin were detected.Myofibroblasts co-expressingα-smooth muscle actin and smoothelin were observed,and their number was slightly increased in parallel with the degree of fibrosis(absent in liver with mild or moderate fibrosis;5%to 10%positive in liver showing severe fibrosis).In cirrhotic septa,numerous myofibroblasts co-expressedα-smooth muscle actin and smoothelin(more than 50%).In hepatocellular carcinomas,the same pattern of expression forα-smooth muscle actin and smoothelin was observed in the stroma reaction surrounding the tumor and around tumoral cell plates.In all pathological liver samples,α-smooth muscle actin and smoothelin were co-expressed in vascular smooth muscle cells.CONCLUSION:During development of advanced liver fibrosis,a subpopulation of myofibroblasts expressing smoothelin may be derived from vascular smooth muscle cells,illustrating the different cellular origins of myofibroblasts. 关 键 词:Smooth MUSCLE CELLS MYOFIBROBLASTS α-smooth MUSCLE ACTIN SMOOTHELIN Fibrosis/cirrhosis Hepatocellular carcinoma
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