Investigation of the effects of Schistosoma mansoni eggs on hepatic stellate cell phenotype

• Main Author: Anthony, Barrie
• Published: University of Salford 2010
• Subjects: 617
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521601

Schistosomiasis is one of the most important helminth infections in man, infecting an estimated 200 million people worldwide leaving 20 million people with severe morbidity and causing 20,000 deaths a year. Of chronically infected patients approximately 8 per cent develop the periportal fibrosis first described by Symmer in 1908 known as clay-pipe-stem fibrosis. Little research has been carried out in the disease with regards to fibrosis alone. The main cell within the liver responsible for fibrosis in a number of liver conditions is the hepatic stellate cell (HSC). This cell is located in the liver sinusoid and is responsible for matrix maintenance and storage of vitamin A within the liver. Upon insult to the liver this cell undergoes a process of transdifferentiation into a myofibroblast responsible for production of a scar like matrix observed in liver fibrosis. This thesis investigates interactions between viable and non-viable schistosome eggs with this cell in an in vitro model developed within this investigation. This model makes use of the HSC human cell line, LX-2. HSC demonstrate dose and time-dependent reduced expression of fibrogenic genes for a-smooth muscle actin, connective tissue growth factor and type I collagen but increased expression of adipogenic peroxisome proliferator-activated receptor y. HSC exhibited elongated fine processes and reduced size, increased accumulation of lipid droplets and reduced expression of a-smooth muscle actin and F-actin stress fibres. Additionally, schistosome eggs prevented the HSC fibrogenic response to exogenous transforming growth factor-p. This supports previous research to suggest that fibrosis observed in schistosomiasis is TGF-3 independent and may additionally explain why myofibroblasts are observed towards the edge of granulomas and not in the immediate vicinity of the eggs themselves. In summary, viable and non- eggs blocked fibrogenesis in HSC, a finding which may have implications for our understanding of the fibrotic pathology in S.mansoni infections.