Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Genes Dev. 2010 Nov 1;24(21):2383-8. doi: 10.1101/gad.1978810.
Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.
尽管 Hippo 信号通路在器官大小控制中的发育作用已得到充分认识，但该途径在组织再生中的作用在很大程度上尚不清楚。在这里，我们使用葡聚糖硫酸钠（DSS）诱导的结肠再生模型来解决这个问题。我们发现，再生隐窝表达升高的 Yes 相关蛋白（YAP）水平。在正常的体内平衡下，YAP 的失活不会引起明显的肠道缺陷，但严重损害 DSS 诱导的肠道再生。相反，YAP 的过度激活会导致 DSS 处理后广泛出现早期息肉形成。因此，YAP 癌蛋白在组织再生中必须受到精细控制，以允许代偿性增殖并防止组织再生程序的内在致癌潜力。
