| Peer-Reviewed

Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway

Received: 13 January 2021     Accepted: 27 January 2021     Published: 30 January 2021
Views:       Downloads:
Abstract

Aim This study was conducted to evaluate the influence of decorin on apoptosis and oxidative stress response upon exposure of human lens epithelial (HLE) cells to high levels of glucose. Methods The HLE cell line (HLEB3) was cultured under various conditions, including normal (5.5 mM) or high glucose (60 mM) medium. Next, 50 nM Decorin was added two hours prior to the addition of high glucose medium. Apoptosis detection was carried out by Western blotting and flow cytometry. Oxidative stress levels were determined by quantifying reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GSH) levels. P38 mitogen-activated protein kinase (MAPK) phosphorylation and rac1 in HLE cells and human lens anterior capsules were evaluated using Western blotting. Knockdown of rac1 and p38 MAPK in HLEB3 cells was achieved using transfection of small-interfering RNAs. Results HLE cells exposed to high levels of glucose underwent oxidative stress and apoptosis, leading to higher proportion of apoptotic cells, ROS generation and a reduction in the bcl/bax ratio, GSH/GSSG ratio, and SOD activity. Additionally, HLEB3 cells exposed to high levels of glucose were found to have increased rac1 and phospho-p38 MAPK. Next, we found that siRNA-mediated knockdown of rac1 or p38 led to a reduction in high-glucose-stimulated cellular apoptosis and oxidative stress. Furthermore, knockdown of rac1 led to a downregulation of p38 MAPK. Interestingly, addition of decorin to HLEB3 cells led to a decrease in apoptosis, oxidative stress, and high-glucose-stimulated induction of rac1 and phospho-p38. Finally, rac1 and p38 levels of capsules were detected to be significantly upregulated in patients with diabetes in comparison to age-matched patients with cataracts. Conclusion The findings indicate that the rac1-p38 pathway plays a role in causing high-glucose-induced injury to the lens epithelial cells. Additionally, these data indicate that decorin can suppress high glucose-stimulated cellular apoptosis and oxidative stress, in part through suppression of the rac1-p38 pathway.

Published in International Journal of Ophthalmology & Visual Science (Volume 6, Issue 1)
DOI 10.11648/j.ijovs.20210601.11
Page(s) 1-9
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

High Glucose, Decorin, Apoptosis, Oxidative Stress

References
[1] Haddad NM, Sun JK, Abujaber S, Schlossman DK, Silva PS. Cataract surgery and its complications in diabetic patients. Seminars in ophthalmology. 2014; 29 (5-6): 329-37. Epub 2014/10/18. doi: 10.3109/08820538.2014.959197. PubMed PMID: 25325858.
[2] Jain AK, Lim G, Langford M, Jain SK. Effect of high-glucose levels on protein oxidation in cultured lens cells, and in crystalline and albumin solution and its inhibition by vitamin B6 and N-acetylcysteine: its possible relevance to cataract formation in diabetes. Free radical biology & medicine. 2002; 33 (12): 1615-21. Epub 2002/12/19. PubMed PMID: 12488130.
[3] Wride MA, Geatrell J, Guggenheim JA. Proteases in eye development and disease. Birth defects research Part C, Embryo today: reviews. 2006; 78 (1): 90-105. Epub 2006/04/20. doi: 10.1002/bdrc.20063. PubMed PMID: 16622853.
[4] Fan H, Sulochana KN, Chong YS, Ge R. Decorin derived antiangiogenic peptide LRR5 inhibits endothelial cell migration by interfering with VEGF-stimulated NO release. The international journal of biochemistry & cell biology. 2008; 40 (10): 2120-8. Epub 2008/04/01. doi: 10.1016/j.biocel.2008.02.009. PubMed PMID: 18373940.
[5] Lala N, Girish GV, Cloutier-Bosworth A, Lala PK. Mechanisms in decorin regulation of vascular endothelial growth factor-induced human trophoblast migration and acquisition of endothelial phenotype. Biology of reproduction. 2012; 87 (3): 59. Epub 2012/06/16. doi: 10.1095/biolreprod.111.097881. PubMed PMID: 22699486.
[6] Grant DS, Yenisey C, Rose RW, Tootell M, Santra M, Iozzo RV. Decorin suppresses tumor cell-mediated angiogenesis. Oncogene. 2002; 21 (31): 4765-77. Epub 2002/07/09. doi: 10.1038/sj.onc.1205595. PubMed PMID: 12101415.
[7] Mohan RR, Tovey JC, Sharma A, Schultz GS, Cowden JW, Tandon A. Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo. PloS one. 2011; 6 (10): e26432. Epub 2011/11/01. doi: 10.1371/journal.pone.0026432. PubMed PMID: 22039486; PubMed Central PMCID: PMCPMC3198476.
[8] Ozay R, Turkoglu E, Gurer B, Dolgun H, Evirgen O, Erguder BI, et al. Does Decorin Protect Neuronal Tissue via Its Antioxidant and Antiinflammatory Activity from Traumatic Brain Injury? An Experimental Study. World neurosurgery. 2017; 97: 407-15. Epub 2016/10/17. doi: 10.1016/j.wneu.2016.09.115. PubMed PMID: 27744073.
[9] Davies JE, Tang X, Denning JW, Archibald SJ, Davies SJ. Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. The European journal of neuroscience. 2004; 19 (5): 1226-42. Epub 2004/03/16. doi: 10.1111/j.1460-9568.2004.03184.x. PubMed PMID: 15016081.
[10] Wang S, Du S, Wu Q, Hu J, Li T. Decorin Prevents Retinal Pigment Epithelial Barrier Breakdown Under Diabetic Conditions by Suppressing p38 MAPK Activation. Investigative ophthalmology & visual science. 2015; 56 (5): 2971-9. Epub 2015/04/02. doi: 10.1167/iovs.14-15874. PubMed PMID: 25829413.
[11] Du S, Wang S, Wu Q, Hu J, Li T. Decorin inhibits angiogenic potential of choroid-retinal endothelial cells by downregulating hypoxia-induced Met, Rac1, HIF-1alpha and VEGF expression in cocultured retinal pigment epithelial cells. Experimental eye research. 2013; 116: 151-60. Epub 2013/09/11. doi: 10.1016/j.exer.2013.08.019. PubMed PMID: 24016866.
[12] Shao JZ, Qi Y, Du SS, Du WW, Li FZ, Zhang FY. In vitro inhibition of proliferation, migration and epithelial-mesenchymal transition of human lens epithelial cells by fasudil. International journal of ophthalmology. 2018; 11 (8): 1253-7. Epub 2018/08/25. doi: 10.18240/ijo.2018.08.02. PubMed PMID: 30140626; PubMed Central PMCID: PMCPMC6090120.
[13] Cui X, Xie PP, Jia PP, Lou Q, Dun G, Li S, et al. Hsf4 counteracts Hsf1 transcription activities and increases lens epithelial cell survival in vitro. Biochimica et biophysica acta. 2015; 1853 (3): 746-55. Epub 2015/01/21. doi: 10.1016/j.bbamcr.2015.01.004. PubMed PMID: 25601714.
[14] Wang GQ, Dang YL, Huang Q, Woo VC, So KF, Lai JS, et al. In Vitro Evaluation of the Effects of Intraocular Lens Material on Lens Epithelial Cell Proliferation, Migration, and Transformation. Current eye research. 2017; 42 (1): 72-8. Epub 2016/06/25. doi: 10.3109/02713683.2016.1156133. PubMed PMID: 27341403.
[15] Rwei P, Alex Gong CS, Luo LJ, Lin MB, Lai JY, Liu HL. In vitro investigation of ultrasound-induced oxidative stress on human lens epithelial cells. Biochemical and biophysical research communications. 2017; 482 (4): 954-60. Epub 2016/11/30. doi: 10.1016/j.bbrc.2016.11.139. PubMed PMID: 27894841.
[16] Acevedo A, Gonzalez-Billault C. Crosstalk between Rac1-mediated actin regulation and ROS production. Free radical biology & medicine. 2018; 116: 101-13. Epub 2018/01/14. doi: 10.1016/j.freeradbiomed.2018.01.008. PubMed PMID: 29330095.
[17] Myant KB, Cammareri P, McGhee EJ, Ridgway RA, Huels DJ, Cordero JB, et al. ROS production and NF-kappaB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell. 2013; 12 (6): 761-73. Epub 2013/05/15. doi: 10.1016/j.stem.2013.04.006. PubMed PMID: 23665120; PubMed Central PMCID: PMCPMC3690525.
[18] Ellenbroek SI, Collard JG. Rho GTPases: functions and association with cancer. Clin Exp Metastasis. 2007; 24 (8): 657-72. Epub 2007/11/15. doi: 10.1007/s10585-007-9119-1. PubMed PMID: 18000759.
[19] Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature. 2005; 436 (7047): 123-7. Epub 2005/07/08. doi: 10.1038/nature03688. PubMed PMID: 16001073; PubMed Central PMCID: PMCPMC2784913.
[20] Witte D, Bartscht T, Kaufmann R, Pries R, Settmacher U, Lehnert H, et al. TGF-beta1-induced cell migration in pancreatic carcinoma cells is RAC1 and NOX4-dependent and requires RAC1 and NOX4-dependent activation of p38 MAPK. Oncol Rep. 2017; 38 (6): 3693-701. Epub 2017/10/19. doi: 10.3892/or.2017.6027. PubMed PMID: 29039574.
[21] Veluthakal R, Kumar B, Mohammad G, Kowluru A, Kowluru RA. Tiam1-Rac1 Axis Promotes Activation of p38 MAP Kinase in the Development of Diabetic Retinopathy: Evidence for a Requisite Role for Protein Palmitoylation. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology. 2015; 36 (1): 208-20. Epub 2015/05/15. doi: 10.1159/000374065. PubMed PMID: 25967961; PubMed Central PMCID: PMCPMC4435616.
[22] Rastogi R, Geng X, Li F, Ding Y. NOX Activation by Subunit Interaction and Underlying Mechanisms in Disease. Frontiers in cellular neuroscience. 2016; 10: 301. Epub 2017/01/26. doi: 10.3389/fncel.2016.00301. PubMed PMID: 28119569; PubMed Central PMCID: PMCPMC5222855.
[23] Du S, Shao J, Xie D, Zhang F. Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway. PLoS One. 2020 Apr 27; 15 (4): e0224251. doi: 10.1371/journal.pone.0224251. PMID: 32339204; PMCID: PMC7185589.
Cite This Article
  • APA Style

    Jingzhi Shao, Shanshan Du, Jingjing Wan, Lirong Zhang, Fengyan Zhang. (2021). Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway. International Journal of Ophthalmology & Visual Science, 6(1), 1-9. https://doi.org/10.11648/j.ijovs.20210601.11

    Copy | Download

    ACS Style

    Jingzhi Shao; Shanshan Du; Jingjing Wan; Lirong Zhang; Fengyan Zhang. Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway. Int. J. Ophthalmol. Vis. Sci. 2021, 6(1), 1-9. doi: 10.11648/j.ijovs.20210601.11

    Copy | Download

    AMA Style

    Jingzhi Shao, Shanshan Du, Jingjing Wan, Lirong Zhang, Fengyan Zhang. Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway. Int J Ophthalmol Vis Sci. 2021;6(1):1-9. doi: 10.11648/j.ijovs.20210601.11

    Copy | Download

  • @article{10.11648/j.ijovs.20210601.11,
      author = {Jingzhi Shao and Shanshan Du and Jingjing Wan and Lirong Zhang and Fengyan Zhang},
      title = {Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway},
      journal = {International Journal of Ophthalmology & Visual Science},
      volume = {6},
      number = {1},
      pages = {1-9},
      doi = {10.11648/j.ijovs.20210601.11},
      url = {https://doi.org/10.11648/j.ijovs.20210601.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijovs.20210601.11},
      abstract = {Aim This study was conducted to evaluate the influence of decorin on apoptosis and oxidative stress response upon exposure of human lens epithelial (HLE) cells to high levels of glucose. Methods The HLE cell line (HLEB3) was cultured under various conditions, including normal (5.5 mM) or high glucose (60 mM) medium. Next, 50 nM Decorin was added two hours prior to the addition of high glucose medium. Apoptosis detection was carried out by Western blotting and flow cytometry. Oxidative stress levels were determined by quantifying reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GSH) levels. P38 mitogen-activated protein kinase (MAPK) phosphorylation and rac1 in HLE cells and human lens anterior capsules were evaluated using Western blotting. Knockdown of rac1 and p38 MAPK in HLEB3 cells was achieved using transfection of small-interfering RNAs. Results HLE cells exposed to high levels of glucose underwent oxidative stress and apoptosis, leading to higher proportion of apoptotic cells, ROS generation and a reduction in the bcl/bax ratio, GSH/GSSG ratio, and SOD activity. Additionally, HLEB3 cells exposed to high levels of glucose were found to have increased rac1 and phospho-p38 MAPK. Next, we found that siRNA-mediated knockdown of rac1 or p38 led to a reduction in high-glucose-stimulated cellular apoptosis and oxidative stress. Furthermore, knockdown of rac1 led to a downregulation of p38 MAPK. Interestingly, addition of decorin to HLEB3 cells led to a decrease in apoptosis, oxidative stress, and high-glucose-stimulated induction of rac1 and phospho-p38. Finally, rac1 and p38 levels of capsules were detected to be significantly upregulated in patients with diabetes in comparison to age-matched patients with cataracts. Conclusion The findings indicate that the rac1-p38 pathway plays a role in causing high-glucose-induced injury to the lens epithelial cells. Additionally, these data indicate that decorin can suppress high glucose-stimulated cellular apoptosis and oxidative stress, in part through suppression of the rac1-p38 pathway.},
     year = {2021}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Decorin Inhibits Glucose-induced Lens Epithelial Cell Apoptosis via Suppressing Rac1-p38 MAPK Signaling Pathway
    AU  - Jingzhi Shao
    AU  - Shanshan Du
    AU  - Jingjing Wan
    AU  - Lirong Zhang
    AU  - Fengyan Zhang
    Y1  - 2021/01/30
    PY  - 2021
    N1  - https://doi.org/10.11648/j.ijovs.20210601.11
    DO  - 10.11648/j.ijovs.20210601.11
    T2  - International Journal of Ophthalmology & Visual Science
    JF  - International Journal of Ophthalmology & Visual Science
    JO  - International Journal of Ophthalmology & Visual Science
    SP  - 1
    EP  - 9
    PB  - Science Publishing Group
    SN  - 2637-3858
    UR  - https://doi.org/10.11648/j.ijovs.20210601.11
    AB  - Aim This study was conducted to evaluate the influence of decorin on apoptosis and oxidative stress response upon exposure of human lens epithelial (HLE) cells to high levels of glucose. Methods The HLE cell line (HLEB3) was cultured under various conditions, including normal (5.5 mM) or high glucose (60 mM) medium. Next, 50 nM Decorin was added two hours prior to the addition of high glucose medium. Apoptosis detection was carried out by Western blotting and flow cytometry. Oxidative stress levels were determined by quantifying reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GSH) levels. P38 mitogen-activated protein kinase (MAPK) phosphorylation and rac1 in HLE cells and human lens anterior capsules were evaluated using Western blotting. Knockdown of rac1 and p38 MAPK in HLEB3 cells was achieved using transfection of small-interfering RNAs. Results HLE cells exposed to high levels of glucose underwent oxidative stress and apoptosis, leading to higher proportion of apoptotic cells, ROS generation and a reduction in the bcl/bax ratio, GSH/GSSG ratio, and SOD activity. Additionally, HLEB3 cells exposed to high levels of glucose were found to have increased rac1 and phospho-p38 MAPK. Next, we found that siRNA-mediated knockdown of rac1 or p38 led to a reduction in high-glucose-stimulated cellular apoptosis and oxidative stress. Furthermore, knockdown of rac1 led to a downregulation of p38 MAPK. Interestingly, addition of decorin to HLEB3 cells led to a decrease in apoptosis, oxidative stress, and high-glucose-stimulated induction of rac1 and phospho-p38. Finally, rac1 and p38 levels of capsules were detected to be significantly upregulated in patients with diabetes in comparison to age-matched patients with cataracts. Conclusion The findings indicate that the rac1-p38 pathway plays a role in causing high-glucose-induced injury to the lens epithelial cells. Additionally, these data indicate that decorin can suppress high glucose-stimulated cellular apoptosis and oxidative stress, in part through suppression of the rac1-p38 pathway.
    VL  - 6
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou, China

  • Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou, China

  • Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou, China

  • Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China

  • Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou, China

  • Sections