Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Inflamm Bowel Dis. 2010 Oct;16(10):1739-50. doi: 10.1002/ibd.21274.
Cux1 is a ubiquitous transcriptional factor that has been associated with cell proliferation, migration, invasion, and differentiation. Cux1 is an effector of the transforming growth factor beta (TGFβ) pathway, PAR(2) receptor signaling, and cellular migration, mechanisms intimately related to inflammatory bowel diseases (IBD).
CD1 mice treated with dextran sulfate sodium (DSS) in drinking water and cultured intestinal epithelial cells were used to determine Cux1 expression under inflammatory conditions. A commercial cDNA library was used to monitor CUX1 expression in IBD patients. The Cux1(ΔHD/ΔHD) hypomorphic mouse model (Cux1ΔHD) treated with DSS in drinking water was used and the disease severity assessed.
Cux1 expression increased in cultured intestinal epithelial cells stimulated with tumor necrosis factor alpha (TNFα), in the mouse intestinal epithelium during experimental colitis and in human IBD patient samples. DSS-induced colitis in Cux1ΔHD mice was more severe according to clinical observations such as weight loss, colon length, and rectal bleeding. Histological observations confirmed an increase of IBD-related morphological changes including ulceration and mucosal infiltration of leukocytes in Cux1ΔHD mice. An increased number of pSer(276)-RelA-positive cells and higher expression levels of proinflammatory cytokines were also measured in the colon of Cux1ΔHD diseased animals. Elevated levels of Cxcl1 were measured before and after DSS-treatment and a greater neutrophilic infiltration was quantified in DSS-treated Cux1ΔHD mice. Finally, mucosal healing was significantly impaired in Cux1ΔHD mice during recovery from DSS treatment.
CUX1 is increased in response to inflammatory stress and its nuclear expression is crucial to protect against DSS-induced colitis and subsequent mucosal healing.
Cux1 是一种普遍存在的转录因子，与细胞增殖、迁移、侵袭和分化有关。Cux1 是转化生长因子 β（TGFβ）途径、PAR（2）受体信号和细胞迁移的效应物，这些机制与炎症性肠病（IBD）密切相关。
使用在饮用水中给予葡聚糖硫酸钠（DSS）的 CD1 小鼠和培养的肠上皮细胞来确定在炎症条件下 Cux1 的表达。使用商业 cDNA 文库来监测 IBD 患者中的 CUX1 表达。使用在饮用水中给予 DSS 的 Cux1（ΔHD/ΔHD）功能减退型小鼠模型（Cux1ΔHD）来评估疾病的严重程度。
在 TNFα 刺激的培养肠上皮细胞、实验性结肠炎期间的小鼠肠上皮和人类 IBD 患者样本中，Cux1 的表达增加。根据体重减轻、结肠长度和直肠出血等临床观察，DSS 诱导的 Cux1ΔHD 小鼠结肠炎更为严重。组织学观察证实了 IBD 相关形态学变化的增加，包括 Cux1ΔHD 小鼠中的溃疡和白细胞黏膜浸润。还在 Cux1ΔHD 患病动物的结肠中测量到更多的 pSer（276）-RelA 阳性细胞和更高水平的促炎细胞因子。在 DSS 处理前后测量到 Cxcl1 水平升高，在 DSS 处理的 Cux1ΔHD 小鼠中量化了更高的中性粒细胞浸润。最后，在从 DSS 治疗中恢复期间，Cux1ΔHD 小鼠的黏膜愈合明显受损。
CUX1 是响应炎症应激而增加的，其核表达对于防止 DSS 诱导的结肠炎和随后的黏膜愈合至关重要。
