Changes in integrin expression during adipocyte differentiation
Changes in integrin expression during adipocyte differentiation
复制标题
DOI：
10.1016/j.cmet.2005.08.006
复制
发表时间：
2005-09-01
期刊：
影响因子：
29
通讯作者：
Saltiel, AR
中科院分区：
文献类型：
--
作者：
Liu, J;DeYoung, SM;Saltiel, AR
3T3-L1 前脂肪细胞需要 cAMP 才能实现最大分化。微阵列分析表明整合素α5和α6受cAMP协调调节。 α 5 表达在脂肪形成过程中逐渐减少，而 α 6 表达增加。前脂肪细胞中α5的过度表达导致增殖增强和分化减弱。相反，α 6 过度表达则没有效果。 GTPase Rac 通常在分化过程中受到抑制。然而，整合素 α 5 的过度表达会增加 Rac 活性。当在前脂肪细胞中过度表达时，组成型活性但非显性失活的 Rac 会抑制分化，这意味着其在 α5 整合素下游在维持前脂肪细胞处于未分化状态中的作用。此外，α6整合素对于基底膜基质胶上生长停滞的前脂肪细胞的聚集至关重要。这种聚集的扰动增强了 Rho 活性并促进生长停滞的前脂肪细胞重新进入细胞周期。这些发现证明了整合素 α 6 在连接形态发生与导致终末分化的信号传导过程中的作用。
3T3-L1 preadipocytes require cAMP for maximal differentiation. Microarray analysis reveals that the integrins alpha 5 and alpha 6 are coordinately regulated by cAMP. alpha 5 expression is gradually diminished during adipogenesis, whereas alpha 6 is increased. Overexpression of alpha 5 in preadipocytes results in enhanced proliferation and attenuated differentiation. Conversely, alpha 6 overexpression is without effect. The GTPase Rac is normally inhibited during differentiation. However, overexpression of integrin alpha 5 increases Rac activity. Constitutively active but not dominant-negative Rac inhibits differentiation when overexpressed in preadipocytes, implying its role downstream of alpha 5 integrin in maintaining preadipocytes in an undifferentiated state. Moreover, alpha 6 integrin is critically involved in clustering growth-arrested preadipocytes on basement membrane Matrigel. Perturbation of such clustering enhances Rho activity and promotes growth-arrested preadipocytes to reenter the cell cycle. These findings demonstrate a role for integrin alpha 6 in connecting morphogenesis with signaling processes leading to terminal differentiation.