期刊
CELL PROLIFERATION
卷 36, 期 6, 页码 307-319出版社
WILEY
DOI: 10.1046/j.1365-2184.2003.00287.x
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To further explore that hepatic stellate cell (HSC) activation results in physiological protection against environmental insult, the profile of differentiation of HSC has been examined upon treatment with ellagic acid (EA), a plant-derived antioxidant that shows multiple protective effects during liver disease. Sparse rat liver cell cultures were grown in media containing EA (3, 6, 30 and 100 mug/ml) and, as controls, without EA, and inspected until day 7 in culture. The cells were double-labelled with antibodies against glial fibrillary acidic protein (GFAP) and smooth muscle alpha-actin (SMAA), marker proteins of quiescent and activated HSC, respectively. In EA-free culture conditions, the quiescent (SMAA(-)/GFAP(+)) HSC transiently acquired a semi-activated (SMAA(+)/GFAP(+)), phenotype and were further transformed into activated (SMAA(+)/GFAP(-)), pleomorphic HSC. Up to a concentration of 30 mug/ml, EA induced an early synthesis of SMAA in all HSC and inhibited their morphologic differentiation and individual growth throughout the culture period. At a concentration of 6 mug/ml, EA supported the semi-activated (SMAA(+)/GFAP(+)) phenotype of HSC throughout the culture period, whereas treatment with high EA concentrations (30 mug/ml) resulted in an early loss of GFAP expression. In conclusion: (i) the uniform response of HSC to EA by mild activation adds functional significance to cellular features preceding the transformation of HSC to myofibroblasts; (ii) the high sensitivity of HSC to EA treatment suggests their involvement in any mechanisms of protection by this antioxidant; (iii) the maintenance of HSC morphology might be one of the factors playing a role in the prevention or slowing down of liver fibrosis; (iv) because the effects of EA are concentration- and time-dependent, an arbitrary usage of this antioxidant is a matter of potential concern; (v) the various patterns of HSC activation observed might correspond to distinct activities of these cells, which, in turn, might lead to different outcomes of liver fibrosis.
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