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The role of Smad3 in mediating mouse hepatic stellate cell activation.

Publication ,  Journal Article
Schnabl, B; Kweon, YO; Frederick, JP; Wang, XF; Rippe, RA; Brenner, DA
Published in: Hepatology
July 2001

Transforming growth factor beta (TGF-beta) is the most potent profibrogenic mediator in liver fibrosis. Although Smad proteins have been identified as intracellular mediators in the TGF-beta signaling pathway, the function of individual Smad proteins remains poorly understood. The aim of this study was to explore the contribution of Smad3 in mediating TGF-beta responses in a model of acute liver injury in vivo and in culture-activated hepatic stellate cells (HSCs). Wild-type, Smad3 heterozygous or Smad3 homozygous knockout mice were treated with a single intragastric administration of CCl(4). After 72 hours, the induction of hepatic collagen alpha1(I) and alpha2(I) messenger RNA (mRNA) levels in Smad3 knockout mice was only 42% and 64%, respectively, of the levels induced in wild-type mice. However, smooth muscle alpha-actin (alpha-SMA) was expressed at a slightly higher level in livers from knockout mice compared with wild-type mice. In culture-activated HSCs from Smad3 knockout mice, collagen alpha1(I) mRNA was 73% of wild-type HSCs, but alpha-SMA expression was the same. HSCs from knockout mice showed a higher proliferation rate than wild-type HSCs. Smad3-deficient HSCs did not form TGF-beta1-induced Smad-containing DNA-binding complexes. In conclusion, (1) maximal expression of collagen type I in activated HSCs requires Smad3 in vivo and in culture; (2) Smad3 is not necessary for HSC activation as assessed by alpha-SMA expression; (3) Smad3 is necessary for inhibition of proliferation of HSCs, which might be TGF-beta-dependent; and (4) Smad3 is required for TGF-beta1-mediated Smad-containing DNA-binding complex formation in cultured HSCs.

Duke Scholars

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

July 2001

Volume

34

Issue

1

Start / End Page

89 / 100

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Trans-Activators
  • Smad3 Protein
  • RNA, Messenger
  • Platelet-Derived Growth Factor
  • Muscle, Smooth
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice
  • Liver Diseases
 

Citation

APA
Chicago
ICMJE
MLA
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Schnabl, B., Kweon, Y. O., Frederick, J. P., Wang, X. F., Rippe, R. A., & Brenner, D. A. (2001). The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology, 34(1), 89–100. https://doi.org/10.1053/jhep.2001.25349
Schnabl, B., Y. O. Kweon, J. P. Frederick, X. F. Wang, R. A. Rippe, and D. A. Brenner. “The role of Smad3 in mediating mouse hepatic stellate cell activation.Hepatology 34, no. 1 (July 2001): 89–100. https://doi.org/10.1053/jhep.2001.25349.
Schnabl B, Kweon YO, Frederick JP, Wang XF, Rippe RA, Brenner DA. The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology. 2001 Jul;34(1):89–100.
Schnabl, B., et al. “The role of Smad3 in mediating mouse hepatic stellate cell activation.Hepatology, vol. 34, no. 1, July 2001, pp. 89–100. Pubmed, doi:10.1053/jhep.2001.25349.
Schnabl B, Kweon YO, Frederick JP, Wang XF, Rippe RA, Brenner DA. The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology. 2001 Jul;34(1):89–100.
Journal cover image

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

July 2001

Volume

34

Issue

1

Start / End Page

89 / 100

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Trans-Activators
  • Smad3 Protein
  • RNA, Messenger
  • Platelet-Derived Growth Factor
  • Muscle, Smooth
  • Mitogen-Activated Protein Kinases
  • Mice, Knockout
  • Mice
  • Liver Diseases