Notch3 regulates the activation of hepatic stellate cells

AIM: To investigate whether Notch signaling is involved in liver fibrosis by regulating the activation of hepatic stellate cells (HSCs). METHODS: Immunohistochemistry was used to detect the expression of Notch3 in fibrotic liver tissues of patients with chronic active hepatitis. The expression of Notch3 in HSC-T6 cells treated or not with transforming growth factor (TGF)-beta 1 was analyzed by immunofluorescence staining. The expression of Notch3 and myofibroblastic marker alpha-smooth muscle actin (alpha-SMA) and collagen I in HSC-T6 cells transfected with pcDNA3.1-N3ICD or control vector were detected by Western blotting and immunofluorescence staining. Moreover, effects of Notch3 knockdown in HSC-T6 by Notch3 siRNA were investigated by Western blotting and immunofluorescence staining. RESULTS: The expression of Notch3 was significantly up-regulated in fibrotic liver tissues of patients with T chronic active hepatitis, but not detected in normal liver tissues. Active Notch signaling was found in HSC-T6 cells. TGF-beta 1 treatment led to up-regulation of Notch3 expression in HSC-T6 cells, and over-expression of Notch3 increased the expression of alpha-SMA and collagen I in HSC-T6 without TGF-beta 1 treatment. Interestingly, transient knockdown of Notch3 decreased the expression of myofibroblastic marker and antagonized TGF-beta 1-induced expression of alpha-SMA and collagen I in HSC-T6. CONCLUSION: Notch3 may regulate the activation of HSCs, and the selective interruption of Notch3 may provide an anti-fibrotic strategy in hepatic fibrosis. (C) 2012 Baishideng. All rights reserved.