Overexpression of Aquaporin-3 Alleviates Hyperosmolarity-Induced Nucleus Pulposus Cell Apoptosis via Regulating the ERK1/2 Pathway.
Overexpression of Aquaporin-3 Alleviates Hyperosmolarity-Induced Nucleus Pulposus Cell Apoptosis via Regulating the ERK1/2 Pathway.
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DOI：
10.1155/2022/1639560
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发表时间：
2022
影响因子：
2.9
通讯作者：
Li, Pei
中科院分区：
文献类型：
--
作者：
Zhang, Zetong;Zhao, Chen;Zhang, Ruijie;Wang, Yiyang;Hu, Yanzhu;Zhou, Qiang;Li, Pei
椎间盘退变（IDD）与渗透压密切相关，渗透压随日常活动而波动，高渗透压可能是髓核（NP）细胞凋亡的一个因素。水通道蛋白-3（AQP-3）属于水通道蛋白家族，主要转运水和其他小分子蛋白，随着椎间盘的老化而减少。 ERK1/2 通路是丝裂原激活蛋白激酶 (MAPK) 的一种，与细胞凋亡相关。本研究旨在探讨AQP-3对高渗透压诱导的NP细胞凋亡的影响，并重点关注ERK1/2信号通路的作用。我们发现高渗透压（550mOsm/kg）可诱导 NP 凋亡，并可同时观察到 AQP-3 的下调和 ERK1/2 的抑制。因此，使用慢病毒增强AQP-3的表达，以比较AQP-3过表达的NP细胞和对照NP细胞的凋亡情况。结果表明，过表达AQP-3可减轻细胞凋亡，并可促进ERK1/2的活性。此外，我们发现抑制剂U0126可以部分加剧AQP-3过表达的NP细胞的凋亡。总之，我们的结果表明，AQP-3 的过度表达可以通过促进 ERK1/2 通路的活性来防止高渗透压诱导的 NP 细胞凋亡。这项研究可能有助于更好地理解 IDD 的病理机制，并将 AQP-3 引入 IDD 治疗方法中。
Intervertebral disc degeneration (IDD) is closely related to osmolarity, which fluctuates with daily activities, and hyperosmolarity may be a contributor to nucleus pulposus (NP) cells apoptosis. Aquaporin-3 (AQP-3) belongs to the family of aquaporins and mainly transports water and other small molecular proteins, which is reduced with the aging of the intervertebral disc. ERK1/2 pathway is one type of mitogen-activated protein kinase (MAPK) and is associated with cellular apoptosis. This study was aimed to investigate the effects of AQP-3 on NP cells apoptosis induced by a hyperosmolarity and focused on the role of the ERK1/2 signaling pathway. We found that NP apoptosis could be induced by hyperosmolarity (550 mOsm/kg), and downregulation of AQP-3 and inhibition of ERK1/2 could be simultaneously observed. Therefore, lentivirus was used to enhance the expression of AQP-3 to compare apoptosis between AQP-3-overexpressed NP cells and the control NP cells. The results showed that apoptosis could be alleviated by overexpression of AQP-3 and the activity of ERK1/2 could also be promoted. Furthermore, we found that the inhibitor U0126 could partly aggravate apoptosis of the AQP-3-overexpressed NP cells. In summary, our results suggested that overexpression of AQP-3 could protect against hyperosmolarity-induced NP cell apoptosis via promoting the activity of the ERK1/2 pathway. This study may shed light on a better understanding of the pathologic mechanism of IDD and bring AQP-3 into the therapeutic approaches for IDD treatment.
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