Department of Biomedical and Clinical Sciences (BKV), Linköping University, s-581 85 Linköping, Sweden.
Wallenberg Centre for Molecular Medicine (WCMM), Linköping University, s-581 85 Linköping, Sweden.
Cells. 2021 Sep 6;10(9):2330. doi: 10.3390/cells10092330.
The gene, which encodes cyclin Y, has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Cyclin Y promotes Wnt/β-catenin signaling and autophagy, which are critical for intestinal epithelial cell (IEC) homeostasis, and may thereby contribute to wound repair in colitis. However, whether cyclin Y has an essential function in IECs is unknown. We, therefore, investigated the epithelial injury response and mucosal regeneration in mice with conditional knock-out of in the intestinal epithelium. We observed that -deficient mice did not exhibit any differences in cell proliferation and disease activity compared to wild-type littermates in the dextran sulfate sodium (DSS) colitis model. Complementary in vitro experiments showed that loss of in model IECs did not affect Wnt signaling, cell proliferation, or autophagy. Additionally, we observed that expression of the cyclin-Y-associated cyclin-dependent kinase (CDK) 14 is exceedingly low specifically in IEC. Collectively, these results suggest that cyclin Y does not contribute to intestinal epithelial homeostasis, possibly due to low levels of specific CDKs in these cells. Thus, it is unlikely that mutations are causatively involved in IBD pathogenesis.
该基因编码细胞周期蛋白 Y，与炎症性肠病（IBD）的发病机制有关。细胞周期蛋白 Y 促进 Wnt/β-catenin 信号通路和自噬，这对于肠道上皮细胞（IEC）的稳态至关重要，并且可能有助于结肠炎的伤口修复。然而，细胞周期蛋白 Y 是否在 IEC 中具有必需的功能尚不清楚。因此，我们研究了条件敲除肠道上皮细胞中的细胞周期蛋白 Y 对上皮损伤反应和黏膜再生的影响。我们观察到，与野生型同窝仔鼠相比，在葡聚糖硫酸钠（DSS）结肠炎模型中，细胞周期蛋白 Y 缺失的小鼠在细胞增殖和疾病活动方面没有任何差异。补充的体外实验表明，模型 IEC 中缺失细胞周期蛋白 Y 不会影响 Wnt 信号通路、细胞增殖或自噬。此外，我们观察到，细胞周期蛋白 Y 相关的细胞周期蛋白依赖性激酶（CDK）14 的表达在 IEC 中特别低。综上所述，这些结果表明细胞周期蛋白 Y 不会促进肠道上皮细胞的稳态，可能是由于这些细胞中特异性 CDK 的水平较低。因此，不太可能是细胞周期蛋白 Y 基因突变导致了 IBD 的发病机制。
