Overexpression of Aquaporin-3 Alleviates Hyperosmolarity-Induced Nucleus Pulposus Cell Apoptosis via Regulating the ERK1/2 Pathway

作者全名："Zhang, Zetong; Zhao, Chen; Zhang, Ruijie; Wang, Yiyang; Hu, Yanzhu; Zhou, Qiang; Li, Pei"

作者地址："[Zhang, Zetong] Hosp PLA, Dept Orthoped, Urumqi 841700, Xinjiang, Peoples R China; [Zhang, Zetong] First Affiliated Hosp Southwest Hosp Army Med Univ, Dept Orthoped, Chongqing 400037, Peoples R China; [Zhao, Chen; Wang, Yiyang; Hu, Yanzhu; Zhou, Qiang; Li, Pei] Third Affiliated Hosp Chongqing Med Univ, Dept Orthoped, Chongqing 400010, Peoples R China; [Zhao, Chen; Wang, Yiyang; Hu, Yanzhu; Zhou, Qiang; Li, Pei] Third Affiliated Hosp Chongqing Med Univ, Tissue Repairing & Biotechnol Res Ctr, Chongqing 401120, Peoples R China; [Zhang, Ruijie] Second Affiliated Hosp Chongqing Med Univ, Chongqing 400010, Peoples R China"

通信作者："Zhou, Q; Li, P (通讯作者)，Third Affiliated Hosp Chongqing Med Univ, Dept Orthoped, Chongqing 400010, Peoples R China.; Zhou, Q; Li, P (通讯作者)，Third Affiliated Hosp Chongqing Med Univ, Tissue Repairing & Biotechnol Res Ctr, Chongqing 401120, Peoples R China."

来源：PAIN RESEARCH & MANAGEMENT

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000791184000001

JCR分区：Q3

影响因子：2.9

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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."

基金机构："National Natural Science Foundation of China [81772378, 81974346]; China Postdoctoral Science Foundation [2021M693925]; Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX0148]; Chongqing Postdoctoral Research Project [2010010005061624]; Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing, China [20200121]; Basic Research Incubation Project of the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China [KY20074]"

基金资助正文："& nbsp;This study was funded by the following: the National Natural Science Foundation of China (No. 81772378 and No. 81974346); project funded by China Postdoctoral Science Foundation (2021M693925). Natural Science Foundation of Chongqing, China (No. cstc2020jcyj-msxmX0148); project supported by Chongqing Postdoctoral Research Project (2010010005061624); Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing, China (No. 20200121); and Basic Research Incubation Project of the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China (KY20074)."