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

Anthony, B

Abstract

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.

Citation

Anthony, B. Investigation of the effects of schistosoma mansoni eggs on hepatic stellate cell phenotype. (Thesis). Salford : University of Salford

• Thesis Type: Thesis
• Deposit Date: Oct 3, 2012
• Award Date: Jan 1, 2010