The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
The Role of Smad3 in Mediating Mouse Hepatic Stellate Cell Activation
Open accessAbstract
Transforming growth factor β (TGF–β) is the most potent profibrogenic mediator in liver fibrosis. Although Smad proteins have been identified as intracellular mediators in the TGF–β 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–β 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 α1(I) and α2(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 α–actin (α–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 α1(I) mRNA was 73% of wild–type HSCs, but α–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–β1-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 α–SMA expression; (3) Smad3 is necessary for inhibition of proliferation of HSCs, which might be TGF–β-dependent; and (4) Smad3 is required for TGF–β1-mediated Smad–containing DNA–binding complex formation in cultured HSCs.
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Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling
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Cited by
Bataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958
Self-citationMyofibroblasts and mechano-regulation of connective tissue remodelling
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Molecular and cellular mechanisms of liver fibrosis and its regression
Kisseleva, T., & Brenner, D. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00372-7 · Cited by 2,024
Self-citationLiver fibrosis – from bench to bedside
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Metadata
- Authors
- Schnabl, B., Kweon, Y. O., Frederick, J. P., Wang, X.-F., Rippe, R. A., & Brenner, D. A.
- Venue
- Hepatology
- Published
- 2001-07
- Volume
- 34
- Issue
- 1
- Pages
- 89-100
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1987291131
- Cited by
- 258
- References
- 72
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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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. https://doi.org/10.1053/jhep.2001.25349
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