首页|Notch3 regulates the activation of hepatic stellate cells
Notch3 regulates the activation of hepatic stellate cells
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维普
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)-β1 was analyzed by immunofluorescence staining.The expression of Notch3 and myofibroblastic marker α-smooth muscle actin (α-SMA) and collagen I in HSC-T6 cells transfected with pcDNA3.1-N3ICD or control vector were detected by Western blotting and immunofiuorescence 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 chronic active hepatitis,but not detected in normal liver tissues.Active Notch signaling was found in HSC-T6 cells.TGF-β1 treatment led to up-regulation of Notch3 expression in HSC-T6 cells,and over-expression of Notch3 increased the expression of α-SMA and collagen I in HSC-T6 without TGF-β1 treatment.Interestingly,transient knockdown of Notch3 decreased the expression of myofibroblastic marker and antagonized TGF-β1-induced expression of α-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.
Department of Hepatology and Infectious Disease, Union Hospital,Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
NETL
NSTL
万方数据
维普
