Department of Urology, Wuxi Second Hospital, Nanjing Medical University, Wuxi, China.
Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):358-364. doi: 10.26355/eurrev_201801_14180.
Obesity emerged as a major public health problem worldwide, and prolonged condition with increased BMI causes various metabolic disorders include the development of kidney cancer. The metabolic changes alter the renal microenvironment and thereby promoting tumor. Hence, detailed studies of genes that regulate these this changes are keen to understand.
Initially, we successfully initiate kidney tumor using prolonged intake of a high-fat diet in Wistar rats, which are confirmed with pathological changes observed through histological sectioning. The expression of Twist2 and CD24 was assessed using Immunohistology and Western Blotting in a different time interval of kidney cancer.
The rats fed with high-fat diet for 8 months shows 1.5 times increased in body mass whereas rats fed with high-fat diet for 16 months shows triple the size when compared with controls. Histological sectioning confirms the development of lesions and proteinaceous casts in 8 months high-fat fed rats, whereas we observed the high proliferative mass of cells in 16 months high-fat fed rats. Interestingly, we also observed elevated expression of Twist2 in initial stages of kidney cancer, which are down-regulated in the latter stages of kidney cancer. The experiments with CD24 shows the gradual increase of the expression of CD24 as a tumor develops to the next level.
The correlation between Twist2 and CD24 expression conclude that Twist2 overexpression in initial stage augments CD24 to express more in the latter stage of kidney cancer. Reversely, the overexpression of CD24 and down-regulation of Twist2 in later stages of kidney cancer suggest the CD24 expression is dependent on Twist2 expression level.
肥胖已成为全球主要的公共卫生问题,BMI 持续增加会导致各种代谢紊乱,包括肾癌的发生。代谢变化改变了肾脏的微环境,从而促进了肿瘤的发生。因此,详细研究调节这些变化的基因对于深入了解肿瘤的发生机制至关重要。
我们最初通过延长 Wistar 大鼠高脂肪饮食的摄入成功地诱导了肾脏肿瘤,这通过组织学切片观察到的病理变化得到了证实。在不同的肾癌时间间隔内,我们使用免疫组织化学和 Western Blotting 评估了 Twist2 和 CD24 的表达。
喂养高脂肪饮食 8 个月的大鼠体重增加了 1.5 倍,而喂养高脂肪饮食 16 个月的大鼠体重增加了 3 倍,与对照组相比。组织学切片证实了 8 个月高脂肪饮食喂养的大鼠中出现了病变和蛋白性铸型,而我们观察到 16 个月高脂肪饮食喂养的大鼠中细胞的高增殖。有趣的是,我们还观察到 Twist2 在肾癌的早期表达升高,而在肾癌的晚期表达下调。CD24 的实验表明,随着肿瘤向更高阶段发展,CD24 的表达逐渐增加。
Twist2 和 CD24 表达之间的相关性表明,在肾癌的早期阶段,Twist2 的过度表达会增强 CD24 的表达,而在肾癌的晚期阶段则下调。相反,在肾癌的晚期阶段,CD24 的过度表达和 Twist2 的下调表明 CD24 的表达依赖于 Twist2 的表达水平。