MAPK/ERK通路
肝星状细胞
体内
SMAD公司
丹参
蛋白激酶A
化学
磷酸化
p38丝裂原活化蛋白激酶
激酶
激活剂(遗传学)
转化生长因子
纤维化
肝纤维化
分子生物学
生物
细胞生物学
内分泌学
内科学
生物化学
医学
病理
受体
生物技术
中医药
替代医学
作者
Chao Wu,Weiyang Chen,Hanyan Ding,Dong Liu,Guangwu Wen,Chong Zhang,Wanpeng Lu,Ming Chen,Yan Yang
出处
期刊:Life Sciences
[Elsevier]
日期:2019-12-01
卷期号:239: 116881-116881
被引量:41
标识
DOI:10.1016/j.lfs.2019.116881
摘要
To investigate anti-liver fibrosis effects of Salvianolic acid B (Sal B) from Salvia miltiorrhiza Bunge involved mitogen-activated protein kinase (MAPK)-mediated transforming growth factor-beta (TGF-β) signaling. Diethylnitrosamine (DEN)-induced liver fibrosis in mice and TGF-β1-activated hepatic stellate cells (HSCs) were established and treated with dosage/concentration-graded Sal B and/or MAPK activator (Vacquinol-1: MKK4-specific activator)/inhibitors (PD98059: ERK-specific inhibitor; SP600125: JNK-specific inhibitor; SB203580: p38-specific inhibitor). Histopathological characteristics and cell migration were assessed, α-SMA, Collagen I and members of TGF-β/MAPK/Smad signal transduction pathway were measured. Results in vivo showed that Sal B alleviated DEN-caused liver fibrosis embodied in ameliorative histopathological characteristics and decreased protein levels of hepatic fibrosis related markers (α-SMA, Collagen I, TGF-β1), its molecular mechanisms of action were correlative with inhibited activation of MAPK and phosphorylation of Smad2/3 at linker regions (P-Smad2/3L) and Smad2 at C-terminal (P-Smad2C) while increased phosphorylation of Smad3 at C-terminal (P-Smad3C). Results in vitro showed that Sal B restrained TGF-β1-induced HSCs activation, Collagen I production and cell migration; Sal B inhibited activation of MAPK and markedly decreased protein levels of P-Smad2/3L and P-Smad2C while slightly increased P-Smad3C in TGF-β1-stimulated HSCs, the expression of PAI-1 was inhibited by Sal B; activating MAPK receded inhibitory effects of Sal B on α-SMA, Collagen I, P-Smad2L and P-Smad3L expression while inhibited activation of MAPK reinforced those. Sal B attenuates liver fibrosis via mediation of TGF-β/Smad and MAPK pathways, especially inhibition of MAPK-mediated P-Smad2/3L signaling, which maybe provides theoretical foundation of Sal B for treating clinically liver fibrosis.
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