The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach
Open accessAbstract
Despite major advances in the understanding of the intimate mechanisms of transforming growth factor-beta (TGF-beta) signaling through the Smad pathway, little progress has been made in the identification of direct target genes. In this report, using cDNA microarrays, we have focussed our attention on the characterization of extracellular matrix-related genes rapidly induced by TGF-beta in human dermal fibroblasts and attempted to identify the ones whose up-regulation by TGF-beta is Smad-mediated. For a gene to qualify as a direct Smad target, we postulated that it had to meet the following criteria: (1) rapid (30 min) and significant (at least 2-fold) elevation of steady-state mRNA levels upon TGF-beta stimulation, (2) activation of the promoter by both exogenous TGF-beta and co-transfected Smad3 expression vector, (3) up-regulation of promoter activity by TGF-beta blocked by both dominant-negative Smad3 and inhibitory Smad7 expression vectors, and (4) promoter transactivation by TGF-beta not possible in Smad3(-/-) mouse embryo fibroblasts. Using this stringent approach, we have identified COL1A2, COL3A1, COL6A1, COL6A3, and tissue inhibitor of metalloproteases-1 as definite TGF-beta/Smad3 targets. Extrapolation of this approach to other extracellular matrix-related gene promoters also identified COL1A1 and COL5A2, but not COL6A2, as novel Smad targets. Together, these results represent a significant step toward the identification of novel, early-induced Smad-dependent TGF-beta target genes in fibroblasts.
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Cites
Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response
Ashcroft, G. S., Yang, X., Glick, A. B., Weinstein, M., Letterio, J. J., Mizel, D. E., Anzano, M., Greenwell-Wild, T., Wahl, S. M., Deng, C., et al. (1999) · Nature Cell Biology · doi:10.1038/12971 · Cited by 911
Cited by
Remodelling the extracellular matrix in development and disease
Bonnans, C., Chou, J., & Werb, Z. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3904 · Cited by 4,367
TGF-β signaling and the fibrotic response
Leask, A., & Abraham, D. J. (2004) · The FASEB Journal · doi:10.1096/fj.03-1273rev · Cited by 2,319
Cardiac Fibrosis: The Fibroblast Awakens
Travers, J. G., Kamal, F. A., Robbins, J., Yutzey, K. E., & Blaxall, B. C. (2016) · Circulation Research · doi:10.1161/circresaha.115.306565 · Cited by 1,596
Daynes, R. A., Araneo, B. A., Ershler, W. B., Maloney, C., Li, G. Z., & Ryu, S. Y. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.12.5219 · Cited by 1,264
Biernacka, A., Dobaczewski, M., & Frangogiannis, N. G. (2011) · Growth Factors · doi:10.3109/08977194.2011.595714 · Cited by 1,161
Metadata
- Authors
- Verrecchia, F., Chu, M.-L., & Mauviel, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 276
- Issue
- 20
- Pages
- 17058-17062
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2134024560
- Cited by
- 664
- References
- 1
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Verrecchia, F., Chu, M.-L., & Mauviel, A. (2001). Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m100754200
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