Autophagy attenuates compression-induced apoptosis of human nucleus pulposus cells via MEK/ERK/NRF1/Atg7 signaling pathways during intervertebral disc degeneration

被引：52

作者：

Li, Shuai ^{[1
]}

Hua, Wenbin ^{[1
]}

Wang, Kun ^{[1
]}

Gao, Yong ^{[1
]}

Chen, Songfeng ^{[2
]}

Liu, Wei ^{[3
]}

Song, Yu ^{[1
]}

Wu, Xinghuo ^{[1
]}

Tu, Ji ^{[1
]}

Kang, Liang ^{[1
]}

Zhao, Kangcheng ^{[1
]}

Xiong, Liming ^{[1
]}

Zhang, Yukun ^{[1
]}

Yang, Cao ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Orthopaed, Wuhan 430022, Hubei, Peoples R China

[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Orthopaed, Zhengzhou 450052, Henan, Peoples R China

[3] First Hosp Wuhan, Dept Orthoped, Wuhan 430022, Hubei, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2018年 / 370卷 / 01期

基金：

美国国家科学基金会;

关键词：

RAS ONCOGENES; IN-VIVO; DISEASE; ACTIVATION; GROWTH; CLASSIFICATION; INHIBITION; MODULATION; SENESCENCE; PROTECTS;

D O I：

10.1016/j.yexcr.2018.06.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Autophagy dysfunction has been observed in intervertebral disc degeneration (IVDD) cells, a main contributing factor to cell death, but the precise role of autophagy during IVDD is still controversial. This study aimed to investigate the role of autophagy involved in the pathogenesis of human IVDD and determine the signal transduction pathways responsible for compression-induced autophagy in human nucleus pulposus (NP) cells. Autophagy, suppressing the induction of apoptosis, was activated in NP cells exposed to compression. Molecular analysis showed that compression promoted the activity of NRF1, a transcription regulator increasing Atg7 expression by binding to its promoter, through activating the Ras/MEK/ERK signaling in NP cells. Loss- and gain-of-function studies demonstrate that NRF1 induced autophagy and dampened the apoptotic response by promoting Atg7 expression in NP cells subjected to compression. This study confirmed that compression-induced autophagy could be induced by Ras via MEK/ERK/NRF1/Atg7 signaling pathways, while inhibiting Ras/MEK/ERK/NRF1/Atg7 signaling pathways attenuated this autophagic process, implicating a promising therapeutic strategy for IVDD.

引用

页码：87 / 97

页数：11

共 57 条

[51]

Mitochondrial Biogenesis Is Impaired in Osteoarthritis Chondrocytes but Reversible via Peroxisome Proliferator-Activated Receptor γ Coactivator 1α [J].