isoprostanes (IsoPs) proved to be mediators of important biological effects and would act through the activation of receptors analogous to those for thromboxane A2 (TP receptors) In a previous work, we provided evidence that IsoPs, generated during carbon tetrachloride-induced hepatic fibrosis, mediate cell proliferation and collagen hyperproduction in hepatic stellate cells (HSC). These effects seem to be mediated by a modified form of isoprostane receptor, homologous to the classic TxA2 binding site, as suggested by binding studies. Moreover, western blotting and immunocytochemistry analysis revealed the expression of TP in HSC both on plasma membranes and within the cells. Further experiments, carried out to clarify the signal transduction pathways, showed that 8-epi-PGF2induced in HSC an increase of Ins(1,4,5)P3. In addition, the treatment of HSC with IsoPs activated ERK1/2, p38 MAPK and cyclin D1. Since these pathways are involved in cell proliferation and collagen gene expression, it is likely that the fibrogenic effects induced by 8-epi-PGF2 in HSC are mediated by these signalling transduction pathways.
Arezzini, B., Monaco, B., Gardi, C., Vecchio, D., Comporti, M. (2008). Fibrogenic effects of isoprostanes on hepatic stellate cells are mediated by TP receptor. In Atti del 1° International Conference on Environmental Stressors in Biology and Medicine (pp.62-62).
Fibrogenic effects of isoprostanes on hepatic stellate cells are mediated by TP receptor
Gardi, C.;Vecchio, D.;Comporti, M.
2008-01-01
Abstract
isoprostanes (IsoPs) proved to be mediators of important biological effects and would act through the activation of receptors analogous to those for thromboxane A2 (TP receptors) In a previous work, we provided evidence that IsoPs, generated during carbon tetrachloride-induced hepatic fibrosis, mediate cell proliferation and collagen hyperproduction in hepatic stellate cells (HSC). These effects seem to be mediated by a modified form of isoprostane receptor, homologous to the classic TxA2 binding site, as suggested by binding studies. Moreover, western blotting and immunocytochemistry analysis revealed the expression of TP in HSC both on plasma membranes and within the cells. Further experiments, carried out to clarify the signal transduction pathways, showed that 8-epi-PGF2induced in HSC an increase of Ins(1,4,5)P3. In addition, the treatment of HSC with IsoPs activated ERK1/2, p38 MAPK and cyclin D1. Since these pathways are involved in cell proliferation and collagen gene expression, it is likely that the fibrogenic effects induced by 8-epi-PGF2 in HSC are mediated by these signalling transduction pathways.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/26593
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