Nicotine Reduces Reactive Oxygen Species and Enhances Cell Proliferation via the α4 Nicotinic Acetylcholine Receptor Subunit in Human Induced Pluripotent Stem Cells
Nicotine Reduces Reactive Oxygen Species and Enhances Cell Proliferation via the α4 Nicotinic Acetylcholine Receptor Subunit in Human Induced Pluripotent Stem Cells
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DOI：
10.1089/scd.2022.0258
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发表时间：
2023-03-30
影响因子：
4
通讯作者：
Sone，Masakatsu
中科院分区：
文献类型：
--
作者：
Ohno，Youichi;Taura，Daisuke;Sone，Masakatsu
吸烟对胎儿发育和干细胞分化的影响尚未完全了解。尽管烟碱乙酰胆碱受体（nAChR）在人体的许多器官中表达，但其在人类诱导多能干细胞（hiPSC）中的意义仍不清楚。在确定hiPSC中nAChR亚基的表达水平后，使用Clariom S Array评估nAChR激动剂尼古丁对未分化hiPSC的影响。我们还确定了尼古丁单独和与nAChR亚基拮抗剂对hiPSC的影响。nAChR α4、α7和β4亚基在hiPSC中强烈表达。cDNA微阵列、基因本体和富集分析表明，将hiPSC暴露于尼古丁改变了与免疫应答、神经系统、致癌作用、细胞分化和细胞增殖相关的基因的表达。特别受影响的是金属硫蛋白，其作用是减少活性氧（ROS）。尼古丁诱导的hiPSC中ROS的减少被α4亚基或非选择性nAChR拮抗剂抵消。尼古丁增加了HiPSC增殖，这种作用也被α4拮抗剂抵消。总之，尼古丁通过hiPSC中的α4 nAChR亚基减少ROS并增强细胞增殖。这些发现为nAChRs对人类干细胞和受精卵的意义提供了新的见解。
The effects of smoking on fetal development and stem cell differentiation are not fully understood. Although nicotinic acetylcholine receptors (nAChRs) are expressed in many organs of the human body, their significance in human induced pluripotent stem cells (hiPSCs) remains unclear. After expression levels of nAChR subunits in hiPSCs were determined, the effects of the nAChR agonist, nicotine, on undifferentiated hiPSCs were evaluated using a Clariom S Array. We also determined the effect of nicotine alone and with a nAChR subunit antagonist on hiPSCs. nAChR α4, α7, and β4 subunits were strongly expressed in hiPSCs. cDNA microarray, gene ontology, and enrichment analyses showed that exposing hiPSCs to nicotine altered expression of genes associated with immune responses, neurological system, carcinogenesis, cell differentiation, and cell proliferation. Particularly affected was metallothionein, which acts to decrease reactive oxygen species (ROS). The nicotine-induced reduction of ROS in hiPSCs was canceled by an α4 subunit or nonselective nAChR antagonist. HiPSC proliferation was increased by nicotine, and this effect, too, was canceled by an α4 antagonist. In conclusion, nicotine reduces ROS and enhances cell proliferation through the α4 nAChR subunit in hiPSCs. These findings provide new insight into the significance of nAChRs on human stem cells and fertilized human ova.