Yang Mingming, Liu Qing, Niu Ting, Kuang Jianbiao, Zhang Xiaohan, Jiang Lingbi, Li Siqi, He Xiaodong, Wang Lijing, Li Jiangchao
Vascular Biology Research Institute, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
Department of Pathology, Zhuhai Branch of Traditional Chinese Medicine Hospital of Guangdong Province, Zhuhai, Guangdong 519015, P.R. China.
Exp Ther Med. 2020 Aug;20(2):1253-1260. doi: 10.3892/etm.2020.8850. Epub 2020 Jun 9.
The p53 gene is well known as a key tumor suppressor gene; it is vital for hematopoietic stem cell differentiation and growth. In the present study, the change of platelets (PLTs) in p53 knockout mice (p53 mice) was investigated. The peripheral blood cell subsets and PLT parameters in p53mice were compared with those in age-matched p53 mice. Bleeding time as well as the alteration of PLT levels, were analyzed with the PLT marker CD41 antibody using flow cytometry. The results revealed that the number of PLTs in p53 mice was significantly lower than that in p53 mice. Bleeding time was prolonged in the peripheral blood of p53 mice compared with that of p53 mice. Furthermore, the related gene expression of the PI3K signaling pathway in the bone marrow of p53 mice was shown to be associated with plateletogenesis. PI3K inhibitor (LY294002) was also used to treat p53 mice, and the results demonstrated that LY294002 revert the change of PLTs in these mice. In summary, PLTs were altered in p53 mice, and the PI3K signaling pathway was involved in that process, suggesting that the p53-dependent PI3K signaling pathway is involved in thrombocytopenia or PLT diseases. PLT number is reduced in p53 deficiency; however, this reduction could be reverted by inhibiting the PI3K pathway.
p53基因作为一种关键的肿瘤抑制基因广为人知；它对造血干细胞的分化和生长至关重要。在本研究中，对p53基因敲除小鼠（p53小鼠）血小板（PLT）的变化进行了研究。将p53小鼠的外周血细胞亚群和PLT参数与年龄匹配的野生型小鼠进行比较。使用PLT标志物CD41抗体通过流式细胞术分析出血时间以及PLT水平的变化。结果显示，p53基因敲除小鼠的PLT数量显著低于野生型小鼠。与野生型小鼠相比，p53基因敲除小鼠外周血的出血时间延长。此外，p53基因敲除小鼠骨髓中PI3K信号通路的相关基因表达与血小板生成有关。还使用PI3K抑制剂（LY294002）处理p53基因敲除小鼠，结果表明LY294002可逆转这些小鼠中PLT的变化。总之，p53基因敲除小鼠的PLT发生了改变，PI3K信号通路参与了这一过程，提示p53依赖的PI3K信号通路与血小板减少症或PLT疾病有关。p53基因缺陷时PLT数量减少；然而，这种减少可通过抑制PI3K途径得以逆转。
