The stellate cells phenotypic transformation in the CCl4- injured liver fibrosis of ICR mice: their desmin immunoreactivity and vitamin A storage.
To elucidate the process of phenotypic transformation of stellate cells which were responsible in the production of collagen fibers, ICR mice were injected subcutaneously with CCl4 twice weekly for 5 weeks and the livers were examined by light and electron microscopy every week. Stellate cells were detected by desmin immunoreaction and vitamin A-autofluorescence. In the first week, following cell necrosis in the pericentral areas, granulomas were formed. Two distinct stellate cell phenotypes were developed i.e. desmin-negative cells in the granuloma and a row of intense desmin-positive cells in its boundaries. Both phenotypes seemed to be derived mostly from perisinusoidal stellate cells and involved in collagen synthesis as evidenced by the presence of reticulin meshwork within the granulomas. The meshwork formation was the initial stage of a new septum formation since in the second week the intense desmin-positive cell rows were closer to the central vein concomitant with the growth of several protrusions to form thin layer septa towards neighboring central or portal veins. The myofibroblast-like cells in the septa with features interposed between stellate cells and myofibroblasts were likely derived from the stellate cells phenotypes. During the transformation of stellate cells, the decline of vitamin A storage was accompanied by the formation of connective tissue septa. The desmin immunoreactivity and vitamin A storage in the stellate cell phenotypes during liver fibrogenesis described in this study may reveal their phenotypic transformation in association with the collagen synthesis.
Lukita-Atmadja
W
W
Department of Anatomy, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Subowo
D000818:Animals; D002251:Carbon Tetrachloride; D003094:Collagen / Q000032:analysis; D003893:Desmin / Q000032:analysis*; D006099:Granuloma / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D010641:Phenotype; D014801:Vitamin A / Q000032:analysis*
D003893:Desmin; D014801:Vitamin A; D003094:Collagen; D002251:Carbon Tetrachloride