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Inhibition of skin development by overexpression of transforming growth factor beta 1 in the epidermis of transgenic mice.
Open accessAbstract
To assess the effect of transforming growth factor beta 1 on the skin in vivo, we have targeted its expression to the epidermis of transgenic mice. To ensure that active TGF-beta 1 was expressed, we used a porcine TGF-beta 1 cDNA with mutations of Cys-223-->Ser and Cys-225-->Ser, which allow constitutive activation. Mice expressing the mutant transforming growth factor beta 1 transgene exhibited a marked phenotype at birth. The skin was very shiny and tautly stretched. These animals were rigid and appeared to be restricted in their ability to move and breathe; death occurred within 24 hr. Histologically, the most prominent features of the skin were a compact orthohyperkeratosis and a reduction in the number of hair follicles. Pulse-labeling studies with 5-bromodeoxyuridine demonstrated a marked reduction in the number of replicating cells in the epidermis and hair follicles. Thus, the macro- and microscopic appearance of these mice, as well as their neonatal lethality, most likely result from inhibition of normal skin development and suppression of epithelial cell proliferation by the overexpression of transforming growth factor beta 1.
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Kulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., & Karlsson, S. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.2.770 · Cited by 1,967
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Cited by
Regulation of Wound Healing by Growth Factors and Cytokines
WERNER, S., & GROSE, R. (2003) · Physiological Reviews · doi:10.1152/physrev.2003.83.3.835 · Cited by 3,629
PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing
Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H., & Tomic‐Canic, M. (2008) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2008.00410.x · Cited by 3,583
Inflammatory cells during wound repair: the good, the bad and the ugly
Martin, P., & Leibovich, S. J. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.09.002 · Cited by 1,340
Cui, W., Fowlis, D. J., Bryson, S., Duffie, E., Ireland, H., Balmain, A., & Akhurst, R. J. (1996) · Cell · doi:10.1016/s0092-8674(00)80127-0 · Cited by 628
Keratins and the Keratinocyte Activation Cycle
Freedberg, I. M., Tomic-Canic, M., Komine, M., & Blumenberg, M. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2001.01327.x · Cited by 567
Metadata
- Authors
- Sellheyer, K., Bickenbach, J. R., Rothnagel, J. A., Bundman, D., Longley, M. A., Krieg, T., Roche, N. S., Roberts, A. B., & Roop, D. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-06
- Volume
- 90
- Issue
- 11
- Pages
- 5237-5241
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2062352917
- Cited by
- 254
- References
- 1
- FWCI
- 25.04
- Type
- journal article
- Language
- en
- Open access
- green
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- Sellheyer, K., Bickenbach, J. R., Rothnagel, J. A., Bundman, D., Longley, M. A., Krieg, T., Roche, N. S., Roberts, A. B., & Roop, D. R. (1993). Inhibition of skin development by overexpression of transforming growth factor beta 1 in the epidermis of transgenic mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.11.5237
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