Abstract：
To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells.
Translation research.
Affiliated Hospital of University.
Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated.
The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification.
Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.
Translation research.
Affiliated Hospital of University.
Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated.
The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification.
Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.
摘要：
目的：探讨H+/K+ATP酶在胃蛋白酶诱导的声带白斑(VCL)细胞增殖中的作用。
方法：翻译研究。
方法：大学附属医院.
方法：免疫组化法检测胃蛋白酶，H+/K+ATPase(ATP4A和ATP4B亚基)在VCL细胞中有不同程度的异型增生。建立VCL细胞的原代培养后，酸化胃蛋白酶对增殖的影响，自噬,研究了VCL细胞的H/K-ATPase分布。
结果：胃蛋白酶的水平，ATP4A,和ATP4B在中度至重度发育不良的VCL组织中明显高于正常组织（p<0.05）；这些水平根据发育不良的严重程度逐渐增加。ATP4A和ATP4B的表达水平与VCL细胞中胃蛋白酶的量显著相关(p<0.01)。酸化胃蛋白酶增强人VCL上皮细胞的增殖和自噬水平。酸化胃蛋白酶对VCL细胞的克隆和自噬促进作用被泮托拉唑部分逆转；这些作用被自噬抑制剂氯喹完全阻断。最后,酸化的胃蛋白酶促进H/K-ATPase和溶酶体在VCL细胞中的共定位；它还介导溶酶体酸化。
结论：胃蛋白酶和H+/K+-ATP酶可能与VCL的进展有关。具体来说,酸化胃蛋白酶可通过促进H+/K+-ATP酶的溶酶体定位来调节溶酶体酸化。
方法：翻译研究。
方法：大学附属医院.
方法：免疫组化法检测胃蛋白酶，H+/K+ATPase(ATP4A和ATP4B亚基)在VCL细胞中有不同程度的异型增生。建立VCL细胞的原代培养后，酸化胃蛋白酶对增殖的影响，自噬,研究了VCL细胞的H/K-ATPase分布。
结果：胃蛋白酶的水平，ATP4A,和ATP4B在中度至重度发育不良的VCL组织中明显高于正常组织（p<0.05）；这些水平根据发育不良的严重程度逐渐增加。ATP4A和ATP4B的表达水平与VCL细胞中胃蛋白酶的量显著相关(p<0.01)。酸化胃蛋白酶增强人VCL上皮细胞的增殖和自噬水平。酸化胃蛋白酶对VCL细胞的克隆和自噬促进作用被泮托拉唑部分逆转；这些作用被自噬抑制剂氯喹完全阻断。最后,酸化的胃蛋白酶促进H/K-ATPase和溶酶体在VCL细胞中的共定位；它还介导溶酶体酸化。
结论：胃蛋白酶和H+/K+-ATP酶可能与VCL的进展有关。具体来说,酸化胃蛋白酶可通过促进H+/K+-ATP酶的溶酶体定位来调节溶酶体酸化。
