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KMID : 0381120230450050657
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Genes and Genomics
2023 Volume.45 No. 5 p.657 ~ p.671
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A20 ameliorates disc degeneration by suppressing mTOR/BNIP3 axis-mediated mitophagy
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Xin Peng
Cong Zhang
Jia-Wei Gao
Feng Wang
Jun-Ping Bao
Zhi-Min Zhou
Rui Sun
Hang-Yu Ji
Kim Hye-Rin
Xiao-Tao Wu
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Abstract
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Background: The pathological mechanism of intervertebral disc degeneration (IDD) is an unanswered question that we are committed to exploring. A20 is an anti-inflammatory protein of nucleus pulposus (NP) cells and plays a protective role in intervertebral disc degeneration.
Objective: This study aims to investigate the molecular mechanism by which A20 attenuates disc degeneration.
Methods: The proteins of interest were measured by immunoblotting, immunofluorescence, ELISA assay, and immunohistochemical technique to conduct related experiments. Immunofluorescence assays and mitochondrial membrane potential (JC-1) were used to assess mitophagy and mitochondrial fitness, respectively.
Results: Here, we demonstrated that A20 promoted mitophagy, attenuated pyroptosis, and inhibited the degradation of the extracellular matrix, consequently significantly ameliorating disc degeneration. Mechanistically, A20 reduces pyroptosis and further suppresses cellular mTOR activity. On the one hand, A20-induced mTOR inhibition triggers BNIP3-mediated mitophagy to ensure mitochondrial fitness under LPS stimulation, as a result of mitigating mitochondrial dysfunction induced by LPS. On the other hand, A20-induced mTOR inhibition reduces the loss of mitochondrial membrane potential and the generation of Mitochondrial ROS.
Conclusion: The study revealed that A20 promotes BNIP3-mediated mitophagy by suppressing mTOR pathway activation against LPS-induced pyroptosis.
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KEYWORD
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A20, BNIP3, Mitophagy, NLRP3, mTOR
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