缺乏αvβ6和αvβ8整合素活性的小鼠重现了Tgfβ1和Tgfβ3基因敲除小鼠的异常表现。
Mice that lack activity of alphavbeta6- and alphavbeta8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice.
作者信息
Aluwihare Poshala, Mu Zhenyu, Zhao Zhicheng, Yu Dawen, Weinreb Paul H, Horan Gerald S, Violette Shelia M, Munger John S
机构信息
Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
出版信息
J Cell Sci. 2009 Jan 15;122(Pt 2):227-32. doi: 10.1242/jcs.035246.
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.
精氨酸 - 甘氨酸 - 天冬氨酸（RGD）结合整合素αvβ6和αvβ8在体内激活潜伏的转化生长因子β1（TGFβ1）和转化生长因子β3（TGFβ3），但尚不确定其他RGD结合整合素，如整合素αvβ5和αvβ3是否激活这些TGFβ亚型。为了确定αvβ6和αvβ8整合素在TGFβ激活中的联合作用，我们通过基因缺失和/或药理学抑制分析了缺乏这两种整合素功能的小鼠。大多数Itgb6-/-;Itgb8-/-胚胎在妊娠中期死亡；存活下来的胚胎会出现腭裂，这与Tgfβ3-/-小鼠中观察到的情况相同。用抗αvβ6整合素抗体处理的Itgb8-/-小鼠会出现严重的自身免疫反应，并且缺乏朗格汉斯细胞，这与Tgfβ1基因敲除小鼠相似。这些结果支持了这样一种模型，即TGFβ3介导的腭融合以及TGFβ1介导的自身免疫抑制和朗格汉斯细胞的产生需要整合素αvβ6和αvβ8，但不需要其他RGD结合整合素作为TGFβ激活剂。
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