| Autor: |
Poshala, Aluwihare, Zhenyu, Mu, Zhicheng, Zhao, Dawen, Yu, Paul H, Weinreb, Gerald S, Horan, Shelia M, Violette, John S, Munger |
| Rok vydání: |
2009 |
| Předmět: |
|
| Zdroj: |
Journal of cell science. 122(Pt 2) |
| ISSN: |
0021-9533 |
| Popis: |
The arginine-glycine-aspartate (RGD)-binding integrins alphavbeta6 and alphavbeta8 activate latent TGFbeta1 and TGFbeta3 in vivo, but it is uncertain whether other RGD-binding integrins such as integrins alphavbeta5 and alphavbeta3 activate these TGFbeta isoforms. To define the combined role of alphavbeta6- and alphavbeta8-integrin in TGFbeta activation, we analyzed mice lacking function of both integrins by means of gene deletion and/or pharmacologic inhibition. Most Itgb6-/-;Itgb8-/- embryos die at mid-gestation; those that survive develop cleft palate-as observed in Tgfb3-/- mice. Itgb8-/- mice treated with an anti-alphavbeta6-integrin antibody develop severe autoimmunity and lack Langerhans cells-similar to Tgfb1-null mice. These results support a model in which TGFbeta3-mediated palate fusion and TGFbeta1-mediated suppression of autoimmunity and generation of Langerhans cells require integrins alphavbeta6 and alphavbeta8 but not other RGD-binding integrins as TGFbeta activators. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
