AIMS: We tested whether transforming growth factor β1 (TGF-β1) signaling plays 
an important role in hepatic stellate cell differentiation fate and investigated 
the role of Jagged1/Notch in this process.
MATERIALS AND METHODS: TGF-β1 was overexpressed and transforming growth factor 
receptor 1 (TGF-β-R1) was knocked down by a lentiviral vector in mouse hepatic 
stellate cells (mHSCs). Transfection efficiency was assessed with 
immunofluorescence, quantitative reverse-transcriptase polymerase chain reaction 
(qRT-PCR) and western blotting. The downstream genes alpha-smooth muscle actin 
(α-SMA), Jagged1 and the differentiation markers alpha-fetoprotein (AFP), 
albumin (ALB), cytokeratin19 (CK19), SRY (sex determining region Y)-box 9 
(SOX9), and hairy and enhancer of split-1 (Hes1) were measured with qRT-PCR and 
western blotting.
KEY FINDINGS: SpHBLV-CMVIE-TGF-β1, pHBLV-CMVIE-GFP, pHBLV-U6-TGF-β-R1 shRNA, and 
pHBLV-U6-RFP were successfully transfected. Over-expression of the TGF-β1 gene 
caused mHSCs to transform into myofibroblasts (MFs) and expression of Jagged1 
and cholangiocyte markers (CK19, SOX9, Hes1) were significantly upregulated 
(P<0.01). Importantly, after blocking TGF-β1 signaling via gene silencing, 
expression of Jagged1 was much reduced, but the mature hepatocyte marker (ALB) 
was obviously increased. In addition, AFP, a hepatic stem cell marker, was 
expressed at the highest level in the control groups.
SIGNIFICANCE: Our findings emphasize that the TGF-β1 signaling pathway regulates 
expression of Jagged1 in mHSCs which is associated with transformation of mHSCs 
into MFs, thus demonstrating a novel mechanism via which TGF-β1 signaling 
controls the differentiation fate of mHSCs through regulation of the 
Jagged1/Notch pathway.