title: Notch3 regulates the activation of hepatic stellate cells.
abstract: OBJECTIVE
  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 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 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.
  
  
  CONCLUSIONS
  Notch3 may regulate the activation of HSCs, and the selective interruption of Notch3 may provide an anti-ﬁbrotic strategy in hepatic ﬁbrosis.
authors.affiliation: Department of Hepatology and Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Yi-Xiong
authors.initials: YX
authors.lastname: Chen
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Weng
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C499374:NOTCH3 protein, human; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D053773:Transforming Growth Factor beta1