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• W3113133742 endingPage "111912" @default.
• W3113133742 startingPage "111912" @default.
• W3113133742 abstract "Smad3 phosphorylation is implicated in hepatic fibro-carcinogenesis. Moreover, Smad3 phospho-isoform pSmad3L and pSmad3C are reversible and antagonistic, and the balance could shift from carcinogenesis to tumor-suppression. pSmad3C has recently assigned to perform a preventative effect against primary liver injury. Salvianolic acid B (Sal B), a component derived from Salvia miltiorrhiza, is empirically used for hepatic diseases. Our prior study clarified that Sal B could delay hepatic fibrosis-carcinoma progression by converting pSmad3L/3C in mice. However, the roles of Smad3 phospho-isoform conversion and antagonism in the anti-hepatocarcinogenic effects of Sal B in pSmad3C- or/and pSmad3L-mutated mice/cells remain vague. Currently, corresponding doses/concentrations of Sal B was co-administrated to pSmad3C+/- mutational mice/plasmids-transfected HepG2 cells. Notably, in vivo functional studies revealed that pSmad3C mutation attenuates Sal B-induced ameliorative effects on histopathological characteristics and decreased serological biomarkers, and potential mechanism involves attenuation of increases in pSmad3C/p21 and decreases in pSmad3L/PAI-1/c-Myc expression. Expectedly, in vitro results showed that up-regulating pSmad3C enhances the inhibitory effects on proliferation, migration and contributes to apoptosis accompanied by a shift of pSmad3L/PAI-1/c-Myc oncogenic to pSmad3C/p21 tumour-suppressive signalling; however, opposite effects occur when upregulated pSmad3L. This study is the first to identify pSmad3C as a key target by which Sal B prevents hepatocarcinogenesis." @default.
• W3113133742 created "2020-12-21" @default.
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• W3113133742 date "2021-01-01" @default.
• W3113133742 modified "2023-09-29" @default.
• W3113133742 title "Smad3 C-terminal phosphorylation site mutation attenuates the hepatoprotective effect of salvianolic acid B against hepatocarcinogenesis" @default.
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• W3113133742 doi "https://doi.org/10.1016/j.fct.2020.111912" @default.
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