HMGB1-induced Autophagy Promotes Extracellular Matrix Degradation Leading to Intervertebral Disc Degeneration

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2020 Oct 12

PMID 33042328

Citations 4

Authors

Biao Fu

Xia Lu

Er-Yang Zhao

Ji-Xin Wang

Si-Min Peng

Affiliations

Soon will be listed here.

Abstract

Intervertebral disc degeneration (IDD) remains a leading cause of adult disability. High mobility group box l (HMGB1) is a nuclear DNA-binding protein and acts as a central mediator of inflammation. The purpose of this study was to investigate the effect of HMGB1 in IDD. In our study, IDD intervertebral disc tissues were collected and nucleus pulposus cells (NPCs) were primarily cultured. The HMGB1 expression and the effect of HMGB1 on NPCs and extracellular matrix and autophagy were all evaluated. Results showed that HMGB1 was markedly overexpressed in IDD (<0.05), and upregulated expression of HMGB1 can inhibit NPC proliferation and promote NPC apoptosis (<0.05), promote extracellular matrix degradation, and activate cell autophagy (<0.05). Therefore, we concluded that HMGB1 was up-regulated in IDD and HMGB1-induced autophagy can promotes extracellular matrix degradation and thus lead to intervertebral disc degeneration. In brief, HMGB1 may serve as a novel diagnostic biomarker and therapeutic target for IDD.

Citing Articles

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References

Bauza M, Gimenez C, Locatelli P, De Lorenzi A, Hnatiuk A, Capogrossi M . High-dose intramyocardial HMGB1 induces long-term cardioprotection in sheep with myocardial infarction. Drug Deliv Transl Res. 2019; 9(5):935-944. DOI: 10.1007/s13346-019-00628-z. View

Liu L, Yang M, Kang R, Wang Z, Zhao Y, Yu Y . HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells. Leukemia. 2010; 25(1):23-31. DOI: 10.1038/leu.2010.225. View

Zigouris A, Alexiou G, Batistatou A, Voulgaris S, Kyritsis A . The role of matrix metalloproteinase 9 in intervertebral disc degeneration. J Clin Neurosci. 2011; 18(10):1424-5. DOI: 10.1016/j.jocn.2011.01.036. View

Jin J, Gong J, Zhao L, Zhang H, He Q, Jiang X . Inhibition of high mobility group box 1 (HMGB1) attenuates podocyte apoptosis and epithelial-mesenchymal transition by regulating autophagy flux. J Diabetes. 2019; 11(10):826-836. DOI: 10.1111/1753-0407.12914. View

Jiang L, Zhang X, Zheng X, Ru A, Ni X, Wu Y . Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: Implications for diabetic intervertebral disc degeneration. J Orthop Res. 2012; 31(5):692-702. DOI: 10.1002/jor.22289. View

Li Y, Cao L, Li J, Sun Z, Liu C, Liang H . Influence of microgravity-induced intervertebral disc degeneration of rats on expression levels of p53/p16 and proinflammatory factors. Exp Ther Med. 2019; 17(2):1367-1373. PMC: 6327631. DOI: 10.3892/etm.2018.7085. View

Paudel Y, Semple B, Jones N, Othman I, Shaikh M . High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches. J Neurochem. 2019; 151(5):542-557. DOI: 10.1111/jnc.14663. View

Liu R, Li T, Zhao G . Cytosolic HMGB1 Mediates Autophagy Activation in an Emulsified Isoflurane Anesthesia Cell Model. Neurochem Res. 2019; 44(5):1090-1100. DOI: 10.1007/s11064-019-02740-5. View

Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L . HMGB1 in health and disease. Mol Aspects Med. 2014; 40:1-116. PMC: 4254084. DOI: 10.1016/j.mam.2014.05.001. View

10.

Tang D, Kang R, Livesey K, Cheh C, Farkas A, Loughran P . Endogenous HMGB1 regulates autophagy. J Cell Biol. 2010; 190(5):881-92. PMC: 2935581. DOI: 10.1083/jcb.200911078. View

11.

Lee W, Cho S, Kim J, Lee C, Lee J, Baek M . Suppressive Effects of Ginsenoside Rh1 on HMGB1-Mediated Septic Responses. Am J Chin Med. 2019; 47(1):119-133. DOI: 10.1142/S0192415X1950006X. View

12.

Urrutia J, Besa P, Campos M, Cikutovic P, Cabezon M, Molina M . The Pfirrmann classification of lumbar intervertebral disc degeneration: an independent inter- and intra-observer agreement assessment. Eur Spine J. 2016; 25(9):2728-33. DOI: 10.1007/s00586-016-4438-z. View

13.

Li L, Zhou Z, Li J, Fang J, Qing Y, Tian T . Diffusion kurtosis imaging provides quantitative assessment of the microstructure changes of disc degeneration: an in vivo experimental study. Eur Spine J. 2019; 28(5):1005-1013. DOI: 10.1007/s00586-019-05924-3. View

14.

Ojo O, Ryu M, Jha A, Unruh H, Halayko A . High-mobility group box 1 promotes extracellular matrix synthesis and wound repair in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2015; 309(11):L1354-66. DOI: 10.1152/ajplung.00054.2015. View

15.

Liu L, Yang M, Kang R, Dai Y, Yu Y, Gao F . HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE. Biochem Biophys Res Commun. 2014; 450(1):851-6. PMC: 4107148. DOI: 10.1016/j.bbrc.2014.06.074. View

16.

Tang D, Kang R, Cheh C, Livesey K, Liang X, Schapiro N . HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene. 2010; 29(38):5299-310. PMC: 2945431. DOI: 10.1038/onc.2010.261. View

17.

Jin H, Wang Q, Wu J, Han X, Qian T, Zhang Z . Baicalein Inhibits the IL-1β-Induced Inflammatory Response in Nucleus Pulposus Cells and Attenuates Disc Degeneration In vivo. Inflammation. 2019; 42(3):1032-1044. DOI: 10.1007/s10753-019-00965-8. View

18.

Takahama M, Akira S, Saitoh T . Autophagy limits activation of the inflammasomes. Immunol Rev. 2017; 281(1):62-73. DOI: 10.1111/imr.12613. View

19.

Huang X, Wang W, Meng Q, Yu L, Fan C, Yu J . Effect of needle diameter, type and volume of contrast agent on intervertebral disc degeneration in rats with discography. Eur Spine J. 2019; 28(5):1014-1022. DOI: 10.1007/s00586-019-05927-0. View

20.

Feng C, Yang M, Lan M, Liu C, Zhang Y, Huang B . ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration. Oxid Med Cell Longev. 2017; 2017:5601593. PMC: 5368368. DOI: 10.1155/2017/5601593. View