Meng Yuan1, Xiaofan Yang1, Dominik Duscher2, Hewei Xiong1, Sen Ren1, Xiang Xu1, Cheng Wang1, Jing Chen1, Yang Liu1, Hans-Günther Machens2, Zhenbing Chen3. 1. Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. 2. Department of Plastic and Hand Surgery, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany. 3. Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: zbchen@hust.edu.cn.
Abstract
AIM: We aim to study the anti-apoptotic effect of microRNA-21-5p (miR-21-5p) in the oxidative stress-induced apoptosis of Schwann cells and the relevant mechanism in this research, laying a foundation for the treatment of peripheral neuropathy (PNP). METHODS AND MATERIALS: The oxidative stress model was established by using hydrogen peroxide (H2O2). ROS level were detected by DCFH-DA (2,7-Dichlorodi-hydrofluorescein diacetate). Western blot and fluorescence staining were used to detect the apoptosis and autophagy level. The miR-21-5p overexpression model was established by transfection of miR-21-5p mimics into RSC96 cells. Five groups of control group, H2O2 group, H2O2 + chloroquine (CQ) group, H2O2 + miR-21-5p mimics group, and H2O2 + miR-21-5p mimics+rapamycin (RAPA) group were included in our experiment. KEY FINDINGS: Compared with control group, miR-21-5p was decreased in H2O2-treated RSC96 cells, while autophagy and apoptosis were both promoted. The result revealed that apoptosis was probably triggered by activation of autophagy in H2O2-treated group. In order to verify the relationship between autophagy and apoptosis more accurately, we used CQ to inhibit autophagy. Compared with H2O2-treated group, autophagy and apoptosis were both weakened in H2O2 + CQ group. Subsequently, we found the antiapoptotic effect of miR-21-5p in this model, overexpression of miR-21-5p prevented cells from being damaged by oxidative stress, it induced the decrease of PTEN and the level of autophagy, leading to decreased level of apoptosis. SIGNIFICANCE: The identified relationship between miR-21-5p, apoptosis, and autophagy promotes us to find a new mechanism to improve the treatment for PNP.
AIM: We aim to study the anti-apoptotic effect of microRNA-21-5p (miR-21-5p) in the oxidative stress-induced apoptosis of Schwann cells and the relevant mechanism in this research, laying a foundation for the treatment of peripheral neuropathy (PNP). METHODS AND MATERIALS: The oxidative stress model was established by using hydrogen peroxide (H2O2). ROS level were detected by DCFH-DA (2,7-Dichlorodi-hydrofluorescein diacetate). Western blot and fluorescence staining were used to detect the apoptosis and autophagy level. The miR-21-5p overexpression model was established by transfection of miR-21-5p mimics into RSC96 cells. Five groups of control group, H2O2 group, H2O2 + chloroquine (CQ) group, H2O2 + miR-21-5p mimics group, and H2O2 + miR-21-5p mimics+rapamycin (RAPA) group were included in our experiment. KEY FINDINGS: Compared with control group, miR-21-5p was decreased in H2O2-treated RSC96 cells, while autophagy and apoptosis were both promoted. The result revealed that apoptosis was probably triggered by activation of autophagy in H2O2-treated group. In order to verify the relationship between autophagy and apoptosis more accurately, we used CQ to inhibit autophagy. Compared with H2O2-treated group, autophagy and apoptosis were both weakened in H2O2 + CQ group. Subsequently, we found the antiapoptotic effect of miR-21-5p in this model, overexpression of miR-21-5p prevented cells from being damaged by oxidative stress, it induced the decrease of PTEN and the level of autophagy, leading to decreased level of apoptosis. SIGNIFICANCE: The identified relationship between miR-21-5p, apoptosis, and autophagy promotes us to find a new mechanism to improve the treatment for PNP.