PI3K/AKT信号通路在椎间盘退变中的研究进展
Research Progress of PI3K/AKT Signaling Pathway in Intervertebral Disc Degeneration
DOI: 10.12677/ACM.2022.12111453, PDF,   
作者: 杨 涛：济宁医学院，山东 济宁；贾 舒, 孟纯阳*：济宁医学院附属医院，山东 济宁
关键词: 下腰痛；椎间盘退变；PI3K/AKT信号通路；分子机制；Low Back Pain； Intervertebral Disc Degeneration； PI3K/AKT Signaling Pathway； Molecular Mechanism
摘要: 下腰痛已成为一个全球关注的公共卫生问题，而椎间盘退行性变被公认为是引起下腰痛的主要原因之一。目前对下腰痛的治疗仅限于在减轻症状，而不能针对椎间盘内潜在的病理生理变化进行根本性治疗。PI3K/AKT通路的激活可以延缓椎间盘退变的进展。本文综述了PI3K/AKT信号通路的激活和负调控的最新研究进展，并着重介绍了不同的治疗方式通过PI3K/AKT信号通路对椎间盘退变产生的积极作用。相信在不久的将来，干预该信号通路有望成为一种有吸引力的治疗策略。
Abstract: Low back pain has become a global public health problem, and intervertebral disc degeneration is recognized as one of the main causes of low back pain. At present, the treatment of low back pain is limited to relieving symptoms, but cannot fundamentally treat the underlying pathophysiological changes in intervertebral discs. The activation of PI3K/AKT pathway can delay the progression of intervertebral disc degeneration. This article reviews the latest research progress in the activation and negative regulation of PI3K/AKT signal pathway, and focuses on the positive effects of different treatments on intervertebral disc degeneration through PI3K/AKT signal pathway. It is believed that intervention in this signaling pathway is expected to become an attractive therapeutic strategy in the near future.
文章引用：杨涛, 贾舒, 孟纯阳. PI3K/AKT信号通路在椎间盘退变中的研究进展[J]. 临床医学进展, 2022, 12(11): 10075-10080. https://doi.org/10.12677/ACM.2022.12111453

参考文献

[1] Vos, T., Allen, C., Arora, M., Barber, R., Bhutta, Z., Brown, A., Carter, A., Casey, D., Khera, S., Tavakkoli, M. and GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (2016) Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 310 Diseases and Injuries, 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015. Lancet, 388, 1545-1602.
[2] Cazzanelli, P. and Wuertz-Kozak, K. (2020) Mi-croRNAs in Intervertebral Disc Degeneration, Apoptosis, Inflammation, and Mechanobiology. International Journal of Molecular Sciences, 21, Article No. 3601. [Google Scholar] [CrossRef] [PubMed]
[3] Dowdell, J., Erwin, M., Choma, T., Vaccaro, A., Iatridis, J. and Cho, S.K. (2017) Intervertebral Disk Degeneration and Repair. Neurosurgery, 80, S46-S54. [Google Scholar] [CrossRef] [PubMed]
[4] Luo, L., Jian, X., Sun, H., Qin, J., Wang, Y., Zhang, J., et al. (2021) Cartilage Endplate Stem Cells Inhibit Intervertebral Disc Degeneration by Releasing Exosomes to Nucleus Pulposus Cells to Activate Akt/Autophagy. Stem Cells, 39, 467-481. [Google Scholar] [CrossRef] [PubMed]
[5] Tong, T., Liu, Z., Zhang, H., Sun, J., Zhang, D., Wang, F., et al. (2019) Age-Dependent Expression of the Vitamin D Receptor and the Protective Effect of Vitamin D Receptor Activation on H2O2-Induced Apoptosis in Rat Intervertebral Disc Cells. The Journal of Steroid Biochemistry and Molecular Biology, 190, 126-138. [Google Scholar] [CrossRef] [PubMed]
[6] Ouyang, Z.H., Wang, W.J., Yan, Y.G., Wang, B. and Lv, G.H. (2017) The PI3K/Akt Pathway: A Critical Player in Intervertebral Disc Degeneration. Oncotarget, 8, 57870-57881. [Google Scholar] [CrossRef] [PubMed]
[7] Xu, S., Li, Y., Lu, Y., Huang, J., Ren, J., Zhang, S., et al. (2018) LZTS2 Inhibits PI3K/AKT Activation and Radioresistance in Nasopharyngeal Carcinoma by Interacting with p85. Cancer Letters, 420, 38-48. [Google Scholar] [CrossRef] [PubMed]
[8] Roy, N.K., Monisha, J., Padmavathi, G., Lalhruaitluanga, H., Kumar, N.S., Singh, A.K., et al. (2019) Isoform-Specific Role of Akt in Oral Squamous Cell Carcinoma. Biomolecules, 9, Article No. 253. [Google Scholar] [CrossRef] [PubMed]
[9] Fu, Y., Li, S. Tong, H., Li, S. and Yan, Y. (2019) WDR13 Promotes the Differentiation of Bovine Skeletal Muscle-Derived Satellite Cells by Affecting PI3K/AKT Signaling. Cell Biology In-ternational, 43, 799-808. [Google Scholar] [CrossRef] [PubMed]
[10] Kawakami, Y., Nishimoto, H., Kitaura, J., Maeda-Yamamoto, M., Kato, R.M., Littman, D.R., et al. (2004) Protein Kinase C βII Regulates Akt Phosphorylation on Ser-473 in a Cell Type- and Stimulus-Specific Fashion. Journal of Biological Chemistry, 279, 47720-47725. [Google Scholar] [CrossRef] 
[11] Nakano, N., Matsuda, S., Ichimura, M., Minami, A., Ogino, M., Murai, T. and Kitagishi, Y. (2017) PI3K/AKT Signaling Mediated by G Protein-Coupled Receptors Is Involved in Neu-rodegenerative Parkinson’s Disease (Review). International Journal of Molecular Medicine, 39, 253-260. [Google Scholar] [CrossRef] [PubMed]
[12] Shen, J.L., Xu, S.X., Zhou, H., Liu, H.Z., Jiang, W., Hao, J., et al. (2017) IL-1β Induces Apoptosis and Autophagy via Mitochondria Pathway in Human Degenerative Nucleus Pulposus Cells. Scientific Reports, 7, Article No. 41067. [Google Scholar] [CrossRef] [PubMed]
[13] Qi, S., Li, C., Kong, X. and Zheng, Q. (2020) Dexmedetomidine Sup-presses Oxidative Stress and Inflammation of Nucleus Pulposus Cells by Activating the PI3K/Akt Signaling Pathway. Pharmazie, 75, 505-509.
[14] Qi, W., Ren, D., Wang, P., Song, Z., Wu, H., Yao, S., et al. (2020) Upregulation of Sirt1 by Tyrosol Suppresses Apoptosis and Inflammation and Modulates Extracellular Matrix Remodeling in Interleu-kin-1β-Stimulated Human Nucleus Pulposus Cells through Activation of PI3K/Akt Pathway. International Im-munopharmacology, 88, Article ID: 106904. [Google Scholar] [CrossRef] [PubMed]
[15] Nan, L.P., Wang, F., Liu, Y., Wu, Z., Feng, X.M., et al. (2020) 6-Gingerol Protects Nucleus Pulposus-Derived Mesenchymal Stem Cells from Oxidative Injury by Activating Autopha-gy. World Journal of Stem Cells, 12, 1603-1622. [Google Scholar] [CrossRef] [PubMed]
[16] Li, Z.L., Wang, J., Deng, X.Y., Huang, D.H., Shao, Z.W. and Ma, K.G. (2021) Compression Stress Induces Nucleus Pulposus Cell Autophagy by Inhibition of the PI3K/AKT/mTOR Pathway and Activation of the JNK Pathway. Connective Tissue Research, 62, 337-349. [Google Scholar] [CrossRef] [PubMed]
[17] He, W.S., Zou, M.X., Yan, Y.G., Yao, N.Z., Chen, W.K., Li, Z., et al. (2020) Interleukin-17A Promotes Human Disc Degeneration by Inhibiting Autophagy through the Activation of the Phosphatidylinositol 3-Kinase/Akt/Bcl2 Signaling Pathway. World Neurosurgery, 143, e215-e223. [Google Scholar] [CrossRef] [PubMed]
[18] Krut, Z., Pelled, G., Gazit, D. and Gazit, Z. (2021) Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration. Cells, 10, Article No. 2241. [Google Scholar] [CrossRef] [PubMed]
[19] Cheng, X.F., Zhang, G.Y., Zhang, L., Hu, Y., Zhang, K., Sun, X.J., et al. (2018) Mesenchymal Stem Cells Deliver Exogenous miR-21 via Exosomes to Inhibit Nucleus Pulposus Cell Apopto-sis and Reduce Intervertebral Disc Degeneration. Journal of Cellular and Molecular Medicine, 22, 261-276. [Google Scholar] [CrossRef] [PubMed]
[20] Yang, S., Zhang, F., Ma, J. and Ding, W. (2020) Intervertebral Disc Ageing and Degeneration: The Antiapoptotic Effect of Oestrogen. Ageing Research Reviews, 57, Article ID: 100978. [Google Scholar] [CrossRef] [PubMed]
[21] Sheng, B., Zhou, J., Liu, X., Yuan, Y., Zhang, Y., Liu, H., et al. (2018) Protective Effect of Estrogen against Calcification in the Cartilage Endplate. International Journal of Clinical and Experimental Pathology, 11, 1660-1666.
[22] Ao, P., Huang, W., Li, J., Wu, T., Xu, L., Deng, Z., et al. (2018) 17β-Estradiol Protects Nucleus Pulposus Cells from Serum Deprivation-Induced Apoptosis and Regulates Expression of MMP-3 and MMP-13 through Promotion of Autophagy. Biochemical and Biophysical Research Communications, 503, 791-797. [Google Scholar] [CrossRef] [PubMed]
[23] Liu, S., Yang, S.D., Huo, X.W., Yang, D.L., Ma, L. and Ding, W.Y. (2018) 17β-Estradiol Inhibits Intervertebral Disc Degeneration by Down-Regulating MMP-3 and MMP-13 and Up-Regulating Type II Collagen in a Rat Model. Artificial Cells, Nanomedicine, and Biotechnology, 46, 182-191. [Google Scholar] [CrossRef] [PubMed]
[24] Saberi, A., Salehi, Z., Naderinabi, B., Ansari, S.H. and Mashayekhi, S. (2018) Genetic Dimension of Intervertebral Disc Degeneration: Polymorphism of Matrix Metallopro-teinase 1 and 3 in the North Iranian Population. Turkish Neurosurgery, 28, 447-453. [Google Scholar] [CrossRef] 
[25] Gao, X.W., Su, X.T., Lu, Z.H. and Ou, J. (2020) 17β-Estradiol Prevents Extracellular Matrix Degradation by Downregulating MMP3 Expression via PI3K/Akt/FOXO3 Pathway. Spine, 45, 292-299. [Google Scholar] [CrossRef] 
[26] Wang, T., Yang, S.D., Liu, S., Wang, H., Liu, H. and Ding, W.Y. (2021) 17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway. Medical Science Monitor, 22, 4312-4322. [Google Scholar] [CrossRef] 
[27] Yang, S.D., Ma, L., Yang, D.L., Ding, W.Y. (2016) Combined Effect of 17β-Estradiol and Resveratrol against Apoptosis Induced by Interleukin-1β in Rat Nucleus Pulposus Cells via PI3K/Akt/Caspase-3 Pathway. PeerJ, 4, e1640. [Google Scholar] [CrossRef] [PubMed]
[28] Wang, J.W., Zhu, L., Shi, P.Z., Wang, P.C., Dai, Y., Wang, Y.X., et al. (2022) 1,25(OH)2D3 Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway. Oxidative Medicine and Cellular Longevity, 2022, Article ID: 1427110. [Google Scholar] [CrossRef] [PubMed]

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