Fig. 9
From: Activation of hepatic stellate cell in Pten null liver injury model
Inhibition of Wnt signal blocks the activation of HSCs. a Downregulation of β-catenin with siRNA against β-catenin led to reduced expression of fibrogenic genes. Left, β-catenin mRNA expression in si-scrambled and si-β-catenin transfected HSCs. Right, protein levels of β-catenin in si-scrambled and si-β-catenin transfected HSCs. *significantly different from the control groups of the same gene at p < 0.05. n = 3 with experiments repeated three times. b The effects of β-catenin knockdown on cell proliferation measured by a MTT assay. n = 3, *p < 0.05. c Representative images of wound healing assay in shβ-catenin knockdown cells vs. controls. d mRNA expression of marker genes of fibrosis in si-scrambled and si-β-catenin transfected HSCs. e LiCl3, an activator of β-catenin, and curcumin, an inhibitor of β-catenin activity, are used to treat primary HSCs at day 2 of culture. Left panel, LiCl3 treatment led to the activation of β-catenin transcriptional activity indicated by an induction of cyclin D1 expression. Middle panel, curcumin treatment led to attenuated cyclin D1 expression, indicating the inhibition of β-catenin transcriptional activity. Right panel, p-GSK3β levels indicate that LiCl3 treatment led to the phosphorylation of GSK3β. f Marker analysis indicates that LiCl3 treatment (left panel) induced expression of fibrotic markers whereas curcumin treatment (right panel) suppressed them. Open bars, vehicle-treated (control); solid bars, either LiCl3- or Curcumin-treated cultures. *significantly different from the control groups of the same gene at p < 0.05. n = 3. g Using a β-catenin inhibitor ICG-001 to block the transcriptional activity of β-catenin reduces the expression of markers for fibrosis except Timp 1. Black bar, DDC-treated Pten null mice; gray bar, Pten mull mice treated with DDC+ICG-001; open bar, vehicle-treated controls. *significantly different from the control groups of the same gene at p < 0.05. n = 3