ReferenceID 6178
Smad3 C-terminal phosphorylation site mutation attenuates the hepatoprotective effect of salvianolic acid B against hepatocarcinogenesis
Food Chem Toxicol
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-suppressi
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Record Fields
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- Reference Id
- 6178
- Evidence Id
- 22768
- Core Evidence Id
- 22768
- Source Reference Id
- 5622
- Herb2 Reference Id
- HBREF006419
- Subject Paper Key
- HBIN042901_33290806
- Pubmed Id
- 33290806
- Doi
- 10.1016/j.fct.2020.111912
- Paper Title
- Smad3 C-terminal phosphorylation site mutation attenuates the hepatoprotective effect of salvianolic acid B against hepatocarcinogenesis
- Paper 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.
- Journal
- Food Chem Toxicol
- Publish Year
- 2021
- Experiment Subject
- mouse; plasmids-transfected hepg2 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Hepatic Fibrosis-carcinoma; Liver Injury; Hepatic Diseases
- Paper Title Cn
- Paper Title En
- Smad3 C-terminal phosphorylation site mutation attenuates the hepatoprotective effect of salvianolic acid B against hepatocarcinogenesis
- Bilingual Status
- semi_complete