Objective     To investiga

te the interactions of transforming growth factor β

1

(TGFβ

1

)/Smads/extracellular signal-regulated kinase (ERK) signaling pathways in hepatic fibrosis and the anti-fibrotic molecular mechanism of Tanshinol in those processes.     Methods     Rat hepatic stellate cells (HSCs) were primarily isolated by in situ liver recirculation and then cultured. MTT colorimetric assay was used to determine the optimal concentration of Tanshinol. HSCs were divided into 3 groups

TGFβ

1

treatment group (5 ng/ml)

TGFβ

1

+ ERK blocking agent (PD98059

100 μmol/L) treatment group

and TGFβ

1

+Tanshinol treatment groups. The proliferation of HSC in each groups was measured by Cell Counting Kit-8 (CCK-8). The protein expressions of α-smooth muscle actin (α-SMA)

and collagen Ⅰ

Ⅲ were detected by immunocytochemical staining. The mRNA expressions of Smad2

3 and 7 in the HSCs were detected by RT-PCR. The phosphorylation levels of Smad2/3 and ERK1/2 proteins and Smad7 protein were detected by Western blotting.     Results    At the treatment of Tanshinol at concentrations of 0.0625

0.125 and 0.25 mmol/L

the proliferation of HSC was significantly inhibited. PD98059 (100 μmol/L) inhibited the HSC proliferation induced by TGFβ

1

and Tanshinol inhibited the TGFβ

1

-induced HSCs proliferation in a dose-dependent manner (P0.01). TGFβ

1

enhanced the expression levels of α-SMA

and collagen Ⅰ and Ⅲ in HSCs (P0.01). PD98059 and Tanshinol decreased these expressions (P0.01). PD98059 depressed the mRNA levels of Smad2

3 and 7 induced by TGFβ

1

(P0.01

0.05). However

Tanshinol only down-regulated the mRNA levels of Smad2 and 3

but up-regulated that of Smad7 (P0.01). PD98059 and Tanshinol decreased the contents of phosphorylated Smad2/3 and ERK1/2 proteins (P0.01)

while they had different effects on the expression of Smad7 protein (P0.01).     Conclusion    TGFβ

1

up-regulates the expressions of Smad2 and 3 mRNA

and phosphorylated proteines to i

nduce the proliferation

activation

and collagen synthesis of HSCs. ERK signaling pathway might be involved in TGFβ

1

-induced Smad mRNA expression and protein phosphorylation. Tanshinol inhibits the signaling pathways of TGFβ/Smad/ERK in hepatic fibrosis.