本研究调查了编码小跨膜蛋白的 Ninjurin1 (Ninj1) 在与性激素相关的结肠炎相关结肠肿瘤发生中的作用。雄性和雌性野生型 (WT) 和 Ninj1 敲除 (KO) 小鼠用氧化偶氮甲烷 (AOM) 和葡聚糖硫酸钠 (DSS) 治疗，有或没有丙酸睾酮 (TP)。在第 2 周（急性结肠炎阶段），Ninj1 KO 表现出雄性和雌性小鼠结肠炎症状的缓解。仅在女性 Ninj1 KO 中，与女性 WT AOM/DSS 组相比，M2 巨噬细胞数量增加，CD8 T 细胞数量减少。在女性 AOM/DSS 组中，与 WT 相比，TP 治疗加剧了 Ninj1 KO 中的结肠缩短。在第 13 周（肿瘤发生阶段），雄性 Ninj1 KO 小鼠的肿瘤较少，但雌性则表现出相似的肿瘤。在WT AOM/DSS组中，雌性比雄性具有更多的M2巨噬细胞和更少的M1巨噬细胞，但这种差异在Ninj1 KO小鼠中不存在。在 Ninj1 KO 与 WT 组中，雌性和雄性 Ninj1 KO 小鼠中促炎介质以及 Ho-1 和 CD8 T 细胞群的表达均下降。在WT组中，AOM/DSS治疗使M2巨噬细胞数量增加，而TP治疗则使M2巨噬细胞数量减少。然而，这两种治疗都没有改变 Ninj1 KO 组的细胞群。这些结果表明Ninj1以睾酮依赖性方式参与结直肠癌的发展，这在男性和女性中是不同的。这凸显了在理解 Ninj1 在癌症发病机制中的作用时考虑性别差异的重要性。© 2024 作者。约翰·威利出版的《国际癌症杂志》

This study investigated the role of Ninjurin1 (Ninj1), encoding a small transmembrane protein, in colitis-associated colon tumorigenesis in relation to sex hormones. Male and female wild-type (WT) and Ninj1 knockout (KO) mice were treated with azoxymethane (AOM) and dextran sulfate sodium (DSS), with or without testosterone propionate (TP). At week 2 (acute colitis stage), Ninj1 KO exhibited an alleviation in the colitis symptoms in both male and female mice. The M2 macrophage population increased and CD8+ T cell population decreased only in the female Ninj1 KO than in the female WT AOM/DSS group. In the female AOM/DSS group, TP treatment exacerbated colon shortening in the Ninj1 KO than in the WT. At week 13 (tumorigenesis stage), male Ninj1 KO mice had fewer tumors, but females showed similar tumors. In the WT AOM/DSS group, females had more M2 macrophages and fewer M1 macrophages than males, but this difference was absent in Ninj1 KO mice. In the Ninj1 KO versus WT group, the expression of pro-inflammatory mediators and Ho-1 and CD8+ T cell populations decreased in both female and male Ninj1 KO mice. In the WT group, M2 macrophage populations were increased by AOM/DSS treatment and decreased by TP treatment. However, neither treatment changed the cell populations in the Ninj1 KO group. These results suggest that Ninj1 is involved in colorectal cancer development in a testosterone-dependent manner, which was different in male and female. This highlights the importance of considering sex disparities in understanding Ninj1's role in cancer pathogenesis.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.