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.

肠再生对于损伤后的功能恢复至关重要，而营养分子可以在此过程中发挥重要作用。在这里，我们发现花生四烯酸（AA）作为肠上皮细胞的直接增殖促进剂，可促进三维培养的类器官和小鼠模型中的小肠再生。如该研究所示，在辐照后再生期间，AA通过上调Ascl2的表达并激活WNT信号传导来正向调节肠上皮细胞的增殖，而对肠上皮细胞的分化则负调节。AA可以作为精细的调节剂，通过激活抗辐射的Msi1 ⁺细胞而不是激活Msi1 ⁺细胞来有效地促进上皮组织修复Lgr5 ⁺细胞，被广泛认为是WNT激活的隐窝基础干细胞。此外，短期AA治疗可在生理条件下维持最佳的肠上皮稳态。结果，AA治疗可以被认为是用于辐射损伤修复和组织再生的潜在疗法。