Department of Biological Structure, University of Washington, Seattle, Washington, USA.
Glia. 2012 Oct;60(10):1579-89. doi: 10.1002/glia.22377. Epub 2012 Jul 6.
Müller glia are normally mitotically quiescent cells, but in certain pathological states they can re-enter the mitotic cell cycle. While several cell cycle regulators have been shown to be important in this process, a role for the tumor suppressor, p53, has not been demonstrated. Here, we investigated a role for p53 in limiting the ability of Müller glia to proliferate in the mature mouse retina. Our data demonstrate that Müller glia undergo a developmental restriction in their potential to proliferate. Retinal explants or dissociated cultures treated with EGF become mitotically quiescent by the end of the second postnatal week. In contrast, Müller glia from adult trp53-/+ or trp53-/- mice displayed a greater ability to proliferate in response to EGF stimulation in vitro. The enhanced proliferative ability of trp53 deficient mice correlates with a decreased expression of the mitotic inhibitor Cdkn1a/p21(cip) and an increase in c-myc, a transcription factor that promotes cell cycle progression. These data show that p53 plays an essential role in limiting the potential of Müller glia to re-enter the mitotic cycle as the retina matures during postnatal development.
Müller 胶质细胞通常处于有丝分裂静止状态，但在某些病理状态下，它们可以重新进入有丝分裂细胞周期。虽然已经证明有几个细胞周期调节剂在这个过程中很重要，但肿瘤抑制因子 p53 的作用尚未得到证明。在这里，我们研究了 p53 在限制成熟小鼠视网膜 Müller 胶质细胞增殖能力方面的作用。我们的数据表明，Müller 胶质细胞在增殖潜力方面存在发育限制。用 EGF 处理的视网膜外植体或分离培养物在出生后第 2 周结束时进入有丝分裂静止状态。相比之下，来自成年 trp53-/+或 trp53-/-小鼠的 Müller 胶质细胞在体外对 EGF 刺激的增殖能力更强。trp53 缺陷型小鼠的增殖能力增强与有丝分裂抑制剂 Cdkn1a/p21(cip)的表达降低以及促进细胞周期进程的转录因子 c-myc 的增加相关。这些数据表明，p53 在限制 Müller 胶质细胞重新进入有丝分裂周期方面发挥着重要作用，因为视网膜在出生后发育过程中成熟。
