Department of Medicine 1, Friedrich-Alexander University, Erlangen, Germany.
Nat Rev Gastroenterol Hepatol. 2020 Sep;17(9):543-556. doi: 10.1038/s41575-020-0326-4. Epub 2020 Jul 10.
The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. As the transit-amplifying progenitors of the intestinal epithelium generate ~300 cells per crypt every day, regulated cell death and sloughing at the apical surface keeps the overall cell number in check. An aberrant increase in the rate of intestinal epithelial cell (IEC) death underlies instances of extensive epithelial erosion, which is characteristic of several intestinal diseases such as inflammatory bowel disease and infectious colitis. Emerging evidence points to a crucial role of necroptosis, autophagy and pyroptosis as important modes of programmed cell death in the intestine in addition to apoptosis. The mode of cell death affects tissue restitution responses and ultimately the long-term risks of intestinal fibrosis and colorectal cancer. A vicious cycle of intestinal barrier breach, misregulated cell death and subsequent inflammation is at the heart of chronic inflammatory and infectious gastrointestinal diseases. This Review discusses the underlying molecular and cellular underpinnings that control programmed cell death in IECs, which emerge during intestinal diseases. Translational aspects of cell death modulation for the development of novel therapeutic alternatives for inflammatory bowel diseases and colorectal cancer are also discussed.
肠上皮细胞的细胞更新率是所有细胞类型中最高的，这一过程受到严格的调控。由于肠上皮的过渡扩增祖细胞每天在每个隐窝中产生约 300 个细胞，因此细胞凋亡和顶端表面的脱落可以控制细胞总数。肠上皮细胞 (IEC) 死亡速度的异常增加是广泛的上皮侵蚀的基础，这是几种肠道疾病的特征，如炎症性肠病和感染性结肠炎。新出现的证据表明，细胞程序性死亡的坏死、自噬和细胞焦亡除了凋亡外，在肠道中也是重要的模式。细胞死亡的方式影响组织修复反应，最终影响肠道纤维化和结直肠癌的长期风险。肠道屏障破坏、细胞死亡失调和随后的炎症之间的恶性循环是慢性炎症性和感染性胃肠道疾病的核心。本综述讨论了控制肠上皮细胞中细胞程序性死亡的潜在分子和细胞基础，这些基础在肠道疾病中显现出来。还讨论了细胞死亡调节的转化方面，以开发炎症性肠病和结直肠癌的新型治疗替代方案。
