下调和上调
粒体自噬
变性(医学)
核心
化学
细胞生物学
自噬
生物
医学
生物化学
细胞凋亡
病理
基因
作者
Dehai Wu,Weijun Huang,Junbin Zhang,He Li,Siyu Chen,Sihan Zhu,Yuan Sang,Kaihua Liu,Gang Hao,Biying Chen,Yang Xu,Bin Liu,Hui Yao
标识
DOI:10.1016/j.ijbiomac.2024.129950
摘要
Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.
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