Hu Wentao, Lu Hong, Wang Shang, Yin Wenhan, Liu Xujie, Dong Lin, Chiu Richard, Shen Li, Lu Wen-Jing, Lan Feng
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
Oncotarget. 2016 Dec 27;7(52):87052-87063. doi: 10.18632/oncotarget.13498.
The expression of intermediate filament Nestin is necessary for the neural progenitor cells (NPCs) to maintain stemness, but the underlying cellular and molecular mechanism remains unclear. In this study, we demonstrated that Nestin is required for the self-renew of NPCs through activating MAPK and EGFR pathways. Knockdown of Nestin by shRNA inhibited cell cycle progression and proliferation in mouse NPCs. Moreover, suppression of Nestin reduced expression of the epidermal growth factor receptor (EGFR) in NPCs and inhibited the mitogenic effects of EGF on these cells. Treatment of NPCs with p38-MAPK inhibitor PD169316 reversed cell cycle arrest caused by the knockdown of Nestin. Our findings indicate that Nestin promotes NPC proliferation via p38-MAPK and EGFR pathways, and reveals the necessity of these pathways in NPCs self-renewal.
中间丝巢蛋白的表达对于神经祖细胞（NPCs）维持干性是必需的，但其潜在的细胞和分子机制仍不清楚。在本研究中，我们证明巢蛋白通过激活丝裂原活化蛋白激酶（MAPK）和表皮生长因子受体（EGFR）通路来促进NPCs的自我更新。用短发夹RNA（shRNA）敲低巢蛋白可抑制小鼠NPCs的细胞周期进程和增殖。此外，抑制巢蛋白可降低NPCs中表皮生长因子受体（EGFR）的表达，并抑制表皮生长因子（EGF）对这些细胞的促有丝分裂作用。用p38-MAPK抑制剂PD169316处理NPCs可逆转因敲低巢蛋白而导致的细胞周期停滞。我们的研究结果表明，巢蛋白通过p38-MAPK和EGFR通路促进NPCs增殖，并揭示了这些通路在NPCs自我更新中的必要性。
