Bowel resection accelerates enterocyte proliferation in the remaining gut that may have suboptimal absorptive and digestive capacity because of proliferation-associated decrease in functional differentiation markers. We hypothesized that although Slfn3 is an important regulator of murine enterocytic differentiation, Slfn3 would have less impact on the bowel resection adaptation where accelerated proliferation takes priority over differentiation. We assessed proliferation, cell shedding, and enterocyte differentiation markers of mucosa from resected and postoperative bowel of wild type (WT) and Slfn3 knockout (Slfn3KO) mice. Villus length and crypt depth were increased in WT mice and was even longer in Slfn3KO mice, while female Slfn3KO mice displayed even deeper crypts than both WT sexes after resection. Mitotic marker, Phh3+, and proliferation marker expression of Lgr5, FoxL1, and PDGFRα were increased after resection in male WT but this effect was blunted in male Slfn3KO mice. Cell shedding regulators Villin1 and TNFα were downregulated in female mice and male WT mice only, while Gelsolin and EGFR increased expression in all mice. Slfn3 expression increased after resection in WT mice but differentiation markers sucrase isomaltase, Dpp4, Glut2, and SGLT1 were all decreased. This suggests that enterocytic differentiation effort is incompatible with a rapid proliferation shift in intestinal adaptation. Slfn3 absence potentiates villus length and crypt depth, suggesting that the differentiating stimulus of Slfn3 signaling may restrain mucosal mass increase through regulating Villin1, Gelsolin, EGFR, TNFα, and proliferation markers. Slfn3 may therefore be an important regulator not only of "normal" enterocytic differentiation but also the response to bowel resection.

中文翻译：

---

50% 肠切除后，Slfn3 缺失会导致性别依赖性修复脆弱性


肠切除加速了剩余肠道中肠细胞的增殖，由于增殖相关的功能分化标记物减少，肠细胞的吸收和消化能力可能不理想。我们假设，虽然 Slfn3 是小鼠肠细胞分化的重要调节因子，但 Slfn3 对肠切除适应的影响较小，其中加速增殖优先于分化。我们评估了野生型 (WT) 和 Slfn3 敲除 (Slfn3KO) 小鼠的切除肠和术后肠粘膜的增殖、细胞脱落和肠细胞分化标记物。 WT 小鼠的绒毛长度和隐窝深度增加，Slfn3KO 小鼠的绒毛长度和隐窝深度更长，而雌性 Slfn3KO 小鼠在切除后显示出比两种 WT 性别更深的隐窝。雄性 WT 切除后，有丝分裂标记物、Ph3+ 以及 Lgr5、FoxL1 和 PDGFRα 增殖标记物的表达增加，但这种效应在雄性 Slfn3KO 小鼠中减弱。细胞脱落调节因子 Villin1 和 TNFα 仅在雌性小鼠和雄性 WT 小鼠中下调，而凝溶胶蛋白和 EGFR 在所有小鼠中表达增加。 WT 小鼠切除后 Slfn3 表达增加，但分化标志物蔗糖酶异麦芽酶、Dpp4、Glut2 和 SGLT1 均下降。这表明肠细胞分化的努力与肠道适应的快速增殖转变是不相容的。 Slfn3 缺失会增强绒毛长度和隐窝深度，表明 Slfn3 信号传导的分化刺激可能通过调节 Villin1、凝溶胶蛋白、EGFR、TNFα 和增殖标志物来抑制粘膜质量增加。因此，Slfn3 可能不仅是“正常”肠细胞分化的重要调节因子，而且也是对肠切除反应的重要调节因子。