Deletion of HO-1 blocks development of B lymphocytes in mice
Deletion of HO-1 blocks development of B lymphocytes in mice
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HO-1 缺失会阻碍小鼠 B 淋巴细胞的发育
DOI：
10.1016/j.cellsig.2019.109378
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发表时间：
2019
影响因子：
4.8
通讯作者：
Wang Jishi
中科院分区：
文献类型：
--
作者：
Zhou Zhen;Ma Dan;Liu Ping;Wang Ping;Wei Danna;Yu Kunling;Li Peifan;Fang Qin;Wang Jishi
B淋巴细胞是组成免疫系统的关键细胞群，可以抵御异常的生物因素。血红素加氧酶-1 （HO-1）在细胞增殖和免疫调节中发挥重要作用，但其对B淋巴细胞发育和生长的影响尚不清楚。其中，HO-1基因敲除（HO-1+/−）小鼠的B淋巴细胞计数明显低于HO-1基因野生型（HO-1WT）小鼠。同时，HO-1+/−小鼠的细胞计数在照射1周后没有恢复，这是由于Pro-B细胞的G0/G1期阻滞和Pre-B细胞的凋亡增加。慢病毒上调HO-1可减轻前b细胞周期阻滞和前b细胞凋亡。为了了解HO-1敲除阻断B淋巴细胞发育的分子机制，我们使用了蛋白-蛋白相互作用网络和Western blot方法。PI3K/AKT信号通路介导HO-1对B淋巴细胞的调控作用。总之，HO-1是B细胞发育的重要转录抑制因子。
B lymphocytes, a key cluster of cells composing the immune system, can protect against abnormal biological factors. Heme oxygenase-1 (HO-1) plays important roles in cell proliferation and immune regulation, but its effects on the development and growth of B lymphocytes are still unknown. Herein, the count of B lymphocytes in HO-1 gene knockout (HO-1+/−) mice was significantly lower than that of the HO-1 gene wild-type (HO-1WT) mice. Meanwhile, the cell count of HO-1+/−mice did not recover after irradiation for one week, due to the G0/G1 phase arrest of Pro-B cells and the augmented apoptosis of Pre-B cells. Up-regulation of HO-1 by lentivirus attenuated the Pro-B cell cycle arrest and Pre-B cell apoptosis. To understand the molecular mechanism by which HO-1 knockout blocked B lymphocyte development, protein-to-protein interaction network and Western blot were used. The PI3K/AKT signaling pathway mediated the regulatory effects of HO-1 on B lymphocytes. In conclusion, HO-1 is a crucial transcriptional repressor for B cell development.