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Galectin-1 Inhibited LPS-Induced Autophagy and Apoptosis of Human Periodontal Ligament Stem Cells

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Abstract

Periodontitis is a widespread human chronic inflammatory disease of the tooth-surrounding tissues, which induces the destruction of periodontium and pathologic loss of teeth among adults. It has been reported that interleukin (IL)-17 was significantly increased in periodontitis patients compared to controls, while galectin-1 (Gal-1) was lower. Interestingly, it is found that Gal-1 treatment reduced systemic IL-17 levels. Hence, the aim of the present study was to explore the effect of Gal-1 on periodontitis development and investigate its underlying mechanism. In this study, Gal-1 was poorly expressed in lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs), and Gal-1 overexpression attenuated the production of inflammatory cytokines induced by LPS. Moreover, Gal-1 overexpression alleviated LPS-induced cell autophagy and apoptosis and reduced the expressions of IL-17A and IL-17R. Interestingly, IL-17A reversed the effect of Gal-1 on cell autophagy, inflammation, and cell apoptosis induced by the LPS challenge. In conclusion, Gal-1 inhibited LPS-induced autophagy and apoptosis of hPDLSC via regulation of IL-17A expression. Therefore, Gal-1 may have promising potential in regenerating periodontium.

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Data Availability

Data are available from the corresponding author on reasonable request.

Abbreviations

hPDLSCs:

human periodontal ligament stem cells

CQ:

chloroquine

3-MA:

3-methyladenine

IL-17:

interleukin-17

Gal-1:

galectin-1

ATCC:

American Type Culture Collection

RT-qPCR:

quantitative real-time PCR

TNF-α:

tumor necrosis factor-α

CCK-8:

cell counting kit-8

References

  1. Liu, Y., C. Liu, A. Zhang, S. Yin, T. Wang, Y. Wang, M. Wang, Y. Liu, Q. Ying, J. Sun, F. Wei, D. Liu, C. Wang, and S. Ge. 2019. Down-regulation of long non-coding RNA MEG3 suppresses osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through miR-27a-3p/IGF1 axis in periodontitis. Aging (Albany NY) 11: 5334–5350.

    Article  CAS  Google Scholar 

  2. Laky, M., I. Anscheringer, L. Wolschner, S. Heber, H. Haririan, X. Rausch-Fan, I. Volf, A. Moritz, and A. Assinger. 2020. Periodontal treatment does not result in detectable platelet activation in vivo. Clinical Oral Investigations 24: 1853–1859.

    Article  Google Scholar 

  3. Ratajczak, J., A. Bronckaers, Y. Dillen, P. Gervois, T. Vangansewinkel, R.B. Driesen, E. Wolfs, I. Lambrichts, and P. Hilkens. 2016. The neurovascular properties of dental stem cells and their importance in dental tissue engineering. Stem Cells International 2016: 9762871.

  4. Wei, W., Y. An, D. Fei, and Q. Wang. 2018. Activation of autophagy in periodontal ligament mesenchymal stem cells promotes angiogenesis in periodontitis. Journal of Periodontology 89: 718–727.

    Article  CAS  Google Scholar 

  5. He, Y., X. Gan, L. Zhang, B. Liu, Z. Zhu, T. Li, J. Zhu, J. Chen, and H. Yu. 2018. CoCl(2) induces apoptosis via a ROS-dependent pathway and Drp1-mediated mitochondria fission in periodontal ligament stem cells. American Journal of Physiology. Cell Physiology 315: C389–C397.

    Article  CAS  Google Scholar 

  6. Liu, J., W. Liu, and H. Yang. 2019. Balancing apoptosis and autophagy for Parkinson’s disease therapy: Targeting BCL-2. ACS Chemical Neuroscience 10: 792–802.

    Article  Google Scholar 

  7. Xu, X., Y. Lai, and Z.C. Hua. 2019. Apoptosis and apoptotic body: Disease message and therapeutic target potentials. Bioscience Reports 39.

  8. Booth, L.A., S. Tavallai, H.A. Hamed, N. Cruickshanks, and P. Dent. 2014. The role of cell signalling in the crosstalk between autophagy and apoptosis. Cellular Signalling 26: 549–555.

    Article  CAS  Google Scholar 

  9. Messer, J.S. 2017. The cellular autophagy/apoptosis checkpoint during inflammation. Cellular and Molecular Life Sciences 74: 1281–1296.

    Article  CAS  Google Scholar 

  10. He, S., Q. Zhou, B. Luo, B. Chen, L. Li, and F. Yan. 2020. Chloroquine and 3-methyladenine attenuates periodontal inflammation and bone loss in experimental periodontitis. Inflammation 43: 220–230.

    Article  CAS  Google Scholar 

  11. Cheng, W.C., F.J. Hughes, and L.S. Taams. 2014. The presence, function and regulation of IL-17 and Th17 cells in periodontitis. Journal of Clinical Periodontology 41: 541–549.

    Article  CAS  Google Scholar 

  12. Chen, X.T., L.L. Chen, J.Y. Tan, D.H. Shi, T. Ke, and L.H. Lei. 2016. Th17 and Th1 lymphocytes are correlated with chronic periodontitis. Immunological Investigations 45: 243–254.

    Article  Google Scholar 

  13. Chen, X.T., J.Y. Tan, L.H. Lei, and L.L. Chen. 2015. Cytokine levels in plasma and gingival crevicular fluid in chronic periodontitis. American Journal of Dentistry 28: 9–12.

    PubMed  Google Scholar 

  14. Li, X., L. Hu, L. Ma, S. Chang, W. Wang, Y. Feng, Y. Xu, J. Hu, C. Zhang, and S. Wang. 2019. Severe periodontitis may influence cementum and dental pulp through inflammation, oxidative stress, and apoptosis. Journal of Periodontology 90: 1297–1306.

    Article  CAS  Google Scholar 

  15. Song, L., J. Tan, Z. Wang, P. Ding, Q. Tang, M. Xia, Y. Wei, and L. Chen. 2019. Interleukinﻗ°∞17A facilitates osteoclast differentiation and bone resorption via activation of autophagy in mouse bone marrow macrophages. Molecular Medicine Reports 19: 4743–4752.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Huang, X.T., W. Liu, Y. Zhou, M. Sun, H.H. Yang, C.Y. Zhang, and S.Y. Tang. 2020. Galectin-1 ameliorates lipopolysaccharide-induced acute lung injury via AMPK-Nrf2 pathway in mice. Free Radical Biology & Medicine 146: 222–233.

    Article  CAS  Google Scholar 

  17. Arda-Pirincci, P., O. Sacan, C. Ozal-Coskun, G. Aykol-Celik, O. Karabulut-Bulan, R. Yanardag, and S. Bolkent. 2020. Galectin-1 exhibits a protective effect against hepatotoxicity induced by dextran sulfate sodium in mice. Human & Experimental Toxicology 39: 423–432.

    Article  CAS  Google Scholar 

  18. Seropian, I. M., G. E. Gonzﺃ­lez, S. M. Maller, D. H. Berrocal, A. Abbate, and G. A. Rabinovich. 2018. Galectin-1 as an emerging mediator of cardiovascular inflammation: Mechanisms and therapeutic opportunities. Mediators of Inflammation 2018:8696543.

  19. Lv, Y., M. Dai, M. Wang, F. Chen, and R. Liu. 2019. Anti-inflammatory property of galectin-1 in a murine model of allergic airway inflammation. Journal of Immunology Research 2019: 9705327.

    Article  Google Scholar 

  20. Lei, T., S. Moos, J. Klug, F. Aslani, S. Bhushan, E. Wahle, S. Frﺃ٦hlich, A. Meinhardt, and M. Fijak. 2018. Galectin-1 enhances TNFﺧ١-induced inflammatory responses in Sertoli cells through activation of MAPK signalling. Scientific Reports 8: 3741.

    Article  Google Scholar 

  21. Mendez-Huergo, S. P., P. F. Hockl, J. C. Stupirski, S. M. Maller, L. G. Morosi, N. A. Pinto, A. M. Berﺃ٣n et al. . 2018. Clinical relevance of galectin-1 and galectin-3 in rheumatoid arthritis patients: Differential regulation and correlation with disease activity. Frontiers in Immunology 9:3057.

  22. İsmail Taşdemir, Huriye Erbak Yılmaz, Figen Narin, Mehmet Sağlam. 2020. Assessment of saliva and gingival crevicular fluid soluble urokinase plasminogen activator receptor (suPAR), galectin-1, and TNF-α levels in periodontal health and disease. J Periodontal Res 55:622-630.

  23. Kogawa, Y., K. Nakajima, K. Sasaguri, N. Hamada, H. Kawasaki, S. Sato, T. Kadoya, and H. Horie. 2011. Oxidized galectin-1 reduces lipopolysaccharide-induced increase of proinflammatory cytokine mRNA in cultured macrophages. Clinical, Cosmetic and Investigational Dentistry 3: 1–8.

    Article  CAS  Google Scholar 

  24. Mab Pereira Corrêa, Frans Eberth Costa Andrade, Alexandre Dantas Gimenes, Cristiane Damas Gil. 2017. Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis. J Mol Med (Berl) 95:1005-1015.

  25. Bui, F.Q., C.L.C. Almeida-da-Silva, B. Huynh, A. Trinh, J. Liu, J. Woodward, H. Asadi, and D.M. Ojcius. 2019. Association between periodontal pathogens and systemic disease. Biomed Journal 42: 27–35.

    Article  Google Scholar 

  26. D’Aiuto, F., N. Gkranias, D. Bhowruth, T. Khan, M. Orlandi, J. Suvan, S. Masi, et al. 2018. Systemic effects of periodontitis treatment in patients with type 2 diabetes: A 12 month, single-centre, investigator-masked, randomised trial. The Lancet Diabetes and Endocrinology 6: 954–965.

    Article  Google Scholar 

  27. Hajishengallis, G. 2015. Periodontitis: From microbial immune subversion to systemic inflammation. Nature Reviews. Immunology 15: 30–44.

    Article  CAS  Google Scholar 

  28. Wang, L., F. Wu, Y. Song, X. Li, Q. Wu, Y. Duan, and Z. Jin. 2016. Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients. Cell Death & Disease 7: e2327.

    Article  CAS  Google Scholar 

  29. Peng, H., B. Liu, T.D. Yves, Y. He, S. Wang, H. Tang, H. Ren, P. Zhao, Z. Qi, and Z. Qin. 2018. Zika virus induces autophagy in human umbilical vein endothelial cells. Viruses 10.

  30. Park, G.B., Y.H. Chung, and D. Kim. 2017. Induction of galectin-1 by TLR-dependent PI3K activation enhances epithelial-mesenchymal transition of metastatic ovarian cancer cells. Oncology Reports 37: 3137–3145.

    Article  CAS  Google Scholar 

  31. Slomiany, B.L., and A. Slomiany. 2017. Role of LPS-elicited signaling in triggering gastric mucosal inflammatory responses to H. pylori: Modulatory effect of ghrelin. Inflammopharmacology 25: 415–429.

    Article  CAS  Google Scholar 

  32. Chung, J., S. Kim, H.A. Lee, M.H. Park, Y.R. Song, and H.S. Na. 2018. Trans-cinnamic aldehyde inhibits Aggregatibacter actinomycetemcomitans-induced inflammation in THP-1-derived macrophages via autophagy activation. Journal of Periodontology 89: 1262–1271.

    Article  CAS  Google Scholar 

  33. An, Y., W. Liu, P. Xue, Y. Zhang, Q. Wang, and Y. Jin. 2016. Increased autophagy is required to protect periodontal ligament stem cells from apoptosis in inflammatory microenvironment. Journal of Clinical Periodontology 43: 618–625.

    Article  Google Scholar 

  34. Xu, L., X. Li, H. Wang, F. Xie, H. Liu, and J. Xie. 2019. Cigarette smoke triggers inflammation mediated by autophagy in BEAS-2B cells. Ecotoxicology and Environmental Safety 184: 109617.

    Article  CAS  Google Scholar 

  35. Chen, Z.H., Y.F. Wu, P.L. Wang, Y.P. Wu, Z.Y. Li, Y. Zhao, J.S. Zhou, C. Zhu, C. Cao, Y.Y. Mao, F. Xu, B.B. Wang, S.A. Cormier, S.M. Ying, W. Li, and H.H. Shen. 2016. Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium. Autophagy 12: 297–311.

    Article  CAS  Google Scholar 

  36. Lin, D., L. Li, Y. Sun, W. Wang, X. Wang, Y. Ye, X. Chen, and Y. Xu. 2014. IL-17 regulates the expressions of RANKL and OPG in human periodontal ligament cells via TRAF6/TBK1-JNK/NF-ﺧﻑB pathways. Immunology 144: 472–485.

    Article  Google Scholar 

  37. Park, Y.D., Y.S. Kim, Y.M. Jung, S.I. Lee, Y.M. Lee, J.B. Bang, and E.C. Kim. 2012. Porphyromonas gingivalis lipopolysaccharide regulates interleukin (IL)-17 and IL-23 expression via SIRT1 modulation in human periodontal ligament cells. Cytokine 60: 284–293.

    Article  CAS  Google Scholar 

  38. Yoo, Y.M., E.M. Jung, and E.B. Jeung. 2019. Rapamycin-induced autophagy decreases Myf5 and MyoD proteins in C2C12 myoblast cells. Toxicology In Vitro 58: 132–141.

    Article  CAS  Google Scholar 

  39. Zhang, W., W. Xu, W. Chen, and Q. Zhou. 2018. Interplay of autophagy inducer rapamycin and proteasome inhibitor MG132 in reduction of foam cell formation and inflammatory cytokine expression. Cell Transplantation 27: 1235–1248.

    Article  Google Scholar 

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Funding

This work was supported by grants from the National Natural Science Foundation of China (NO. 81701008); Key research and development program of Shandong Province (NO. 2019GSF108187, 2019GSF108046); Guangdong Basic and Applied Basic Research Foundation (NO. 2020A1515010150); and Students Research Fund of Shandong University (NO.2019298).

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Authors and Affiliations

  1. Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 West Wenhua Road, Jinan, Shandong, 250012, People’s Republic of China

    Jiahao Zhang, Wei Ren, Rui Zhang, Zhaoli Geng, Xinyi Xu, Chunpeng Liu, Dongxu Liu & Yi Liu

  2. Changle People’s Hospital, Weifang, Shandong, 262400, People’s Republic of China

    Xiaohong Dong

  3. Qufu Stomatological Hospital, Jining, Shandong, 273100, People’s Republic of China

    Qianqian Yan

  4. Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, 250012, People’s Republic of China

    Xinyi Jiang

  5. Department of Orthodontics, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China

    Shijie Zhang

  6. Shenzhen Research Institute of Shandong University, Shenzhen, Guangdong, 518057, People’s Republic of China

    Yi Liu

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  1. Jiahao Zhang
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Contributions

The study was designed, and funding was provided by D.L. and Y.L.; the study was conducted, and the manuscript was prepared by J.Z., D.L., and Y.L.; most experiments were performed by J.Z., X.D., Q.Y., W.R., R.Z., and X.J.; the data were studied by Z.G., X.X., C.L., and S.Z. The final manuscript was read and approved by all authors.

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Correspondence to Dongxu Liu or Yi Liu.

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Zhang, J., Dong, X., Yan, Q. et al. Galectin-1 Inhibited LPS-Induced Autophagy and Apoptosis of Human Periodontal Ligament Stem Cells. Inflammation 44, 1302–1314 (2021). https://doi.org/10.1007/s10753-021-01417-y

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  • DOI: https://doi.org/10.1007/s10753-021-01417-y

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