Key Laboratory of Functional Dairy, Beijing Laboratory of Food Quality and Safety, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China.
State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
Stem Cell Reports. 2020 Aug 11;15(2):374-388. doi: 10.1016/j.stemcr.2020.06.009. Epub 2020 Jul 9.
Intestinal regeneration is crucial for functional restoration after injury, and nutritional molecules can play an important role in this process. Here, we found that arachidonic acid (AA) serves as a direct proliferation promoter of intestinal epithelial cells that facilitates small intestinal regeneration in both three-dimensional cultured organoids and mouse models. As shown in the study, during post-irradiation regeneration, AA positively regulates intestinal epithelial cell proliferation by upregulating the expression of Ascl2 and activating WNT signaling, but negatively regulates intestinal epithelial cell differentiation. AA acts as a delicate regulator that efficiently facilitates epithelial tissue repair by activating radiation-resistant Msi1 cells rather than Lgr5 cells, which are extensively considered WNT-activated crypt base stem cells. Additionally, short-term AA treatment maintains optimal intestinal epithelial homeostasis under physiological conditions. As a result, AA treatment can be considered a potential therapy for irradiation injury repair and tissue regeneration.
肠道再生对于损伤后的功能恢复至关重要，而营养分子可以在这个过程中发挥重要作用。在这里，我们发现花生四烯酸（AA）可作为肠上皮细胞的直接增殖促进剂，促进三维培养类器官和小鼠模型中的小肠再生。如研究所示，在辐照后再生过程中，AA 通过上调 Ascl2 的表达和激活 WNT 信号来正向调节肠上皮细胞增殖，但负向调节肠上皮细胞分化。AA 作为一种微妙的调节剂，通过激活辐射抗性的 Msi1 细胞而不是广泛认为的 WNT 激活的隐窝底部干细胞 Lgr5 细胞，有效地促进上皮组织修复。此外，短期 AA 处理在生理条件下维持最佳的肠上皮细胞稳态。因此，AA 处理可被视为辐照损伤修复和组织再生的一种潜在治疗方法。
