Brief Article
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World J Gastroenterol. Mar 28, 2012; 18(12): 1397-1403
Published online Mar 28, 2012. doi: 10.3748/wjg.v18.i12.1397
Notch3 regulates the activation of hepatic stellate cells
Yi-Xiong Chen, Zhi-Hong Weng, Shu-Ling Zhang
Yi-Xiong Chen, Zhi-Hong Weng, Shu-Ling Zhang, Department of Hepatology and Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Chen YX and Weng ZH contributed equally to this work; Weng ZH designed the research; Chen YX and Zhang SL performed the research and analyzed the data; Weng ZH and Chen YX wrote the manuscript; Zhang SL revised and approved the article to be published.
Supported by The National Natural Science Foundation of China, No. 30900663
Correspondence to: Shu-Ling Zhang, Professor, Department of Hepatology and Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. zhangshul2010@126.com
Telephone: +86-27-85726783 Fax: +86-27-85356369
Received: July 8, 2011
Revised: September 30, 2011
Accepted: January 7, 2012
Published online: March 28, 2012
Abstract

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 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.

CONCLUSION: Notch3 may regulate the activation of HSCs, and the selective interruption of Notch3 may provide an anti-fibrotic strategy in hepatic fibrosis.

Keywords: Notch signaling, Myofibroblast, Liver fibrosis, Hepatic stellate cells, siRNA