Back to Search
Start Over
[Effect of Notch signaling on the activation of hepatic stellate cells].
- Source :
-
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology [Zhonghua Gan Zang Bing Za Zhi] 2012 Sep; Vol. 20 (9), pp. 677-82. - Publication Year :
- 2012
-
Abstract
- Objective: To investigate whether Notch signaling is activated in hepatic stellate cells (HSCs), and to determine whether manipulation of the Notch signaling pathway can effect the activation of HSCs.<br />Methods: The expression of Notch signaling components in unactivated or TGF-b1-activated HSC-T6 cells was detected by Taqman Probe-based gene expression analysis. Differential expression of Notch3 and Jagged1 was detected by immunofluorescence analysis. Notch3-mediated expression of the myofibroblastic markers, a-SMA and collagen I, was detected in HSC-T6 cells transfected with pcDNA3.1-N3ICD or Notch3 siRNA by Western blotting.<br />Results: Notch signaling components were expressed in both unactivated and activated HSC-T6 cells, but the TGF-b1-treated cells showed significantly higher expression levels of Jagged1 (3.9-fold, F = 2543.482), Notch3 (4.2-fold, F = 287.982), and HES1 (3.2-fold, F = 1719.851). Transfection-mediated over-expression of Notch3 led to significantly increased expression of a-SMA (6.8-fold, t = 13.157) and collagen I (5.5-fold, t = 9.810) (both P less than 0.01). Transient knock-down of Notch3 expression by siRNA decreased expression of the myofibroblastic markers (a-SMA by approximately 90%, t = 19.863 and collagen I by 84%, t = 10.376; both, P less than 0.01). Moreover, knock-down of Notch3 antagonized the TGF-b1-induced expression of a-SMA and collagen I.<br />Conclusion: Notch signaling may participate in liver fibrogenesis by regulating HSC activation. Selective interruption of Notch3 may represent a new anti-fibrotic strategy to treat liver fibrosis.
- Subjects :
- Animals
Calcium-Binding Proteins genetics
Calcium-Binding Proteins metabolism
Cell Line
Intercellular Signaling Peptides and Proteins genetics
Intercellular Signaling Peptides and Proteins metabolism
Jagged-1 Protein
Membrane Proteins genetics
Membrane Proteins metabolism
RNA, Messenger genetics
Rats
Receptor, Notch3
Receptors, Notch genetics
Serrate-Jagged Proteins
Hepatic Stellate Cells metabolism
RNA, Small Interfering
Receptors, Notch metabolism
Signal Transduction
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1007-3418
- Volume :
- 20
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 23207232
- Full Text :
- https://doi.org/10.3760/cma.j.issn.1007-3418.2012.09.008