| Peer-Reviewed

Involvement of ER Stress in Human Primary Pterygium

Received: 13 June 2019     Accepted: 2 July 2019     Published: 11 July 2019
Views:       Downloads:
Abstract

Purpose: The aim of this study was to investigate the ER stress activation in human primary pterygium. Methods and materials: Human primary pterygium or normal Tenon's capsule tissues were obtained from patients with primary pterygium following surgical excision or from normal human fresh cadaver eyes. The tissues were processed within 2 hours. The mRNA or protein specimens were extracted from those tissues for analysis, cryosections of those tissues were prepared for immunohistochemical staining. The mRNA levels of endoplasmic reticulum (ER) stress-related factors in those tissues were detected by qPCR analysis and the related proteins levels were detected by qPCR analysis and immunohistochemical staining or western blotting. Results: The ER stress-related gene transcription levels of GRP78,spliced XBP-1, ATF4 and ATF6 and the protein expression levels of GRP78, p-IRE1α, p-eIF2α and ATF6 were all increased in the human primary pterygium tissues when compared with the normal control tissues. Conclusion: The results in this study suggest that the three unfolded protein response pathways are all activated in the human primary pterygium tissues, which indicates that the ER stress is involved in the progression of pterygium, and also suggests a potential mechanism of ER stress-induced inflammation in the human primary pterygium tissues.

Published in International Journal of Ophthalmology & Visual Science (Volume 4, Issue 2)
DOI 10.11648/j.ijovs.20190402.11
Page(s) 30-36
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), 2019. Published by Science Publishing Group

Keywords

Primary Pterygium, Endoplasmic Reticulum Stress, Unfolded Protein Response, Inflammation, UPR Pathway Activation

References
[1] Pluquet O, Pourtier A, Abbadie C. The unfolded protein response and cellular senescence. A review in the theme: cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. Am J Physiol Cell Physiol. 2015; 308 (6): C415-25. doi: 10.1152/ajpcell.00334.2014. PubMed PMID: 25540175.
[2] Reid DW, Nicchitta CV. Diversity and selectivity in mRNA translation on the endoplasmic reticulum. Nat Rev Mol Cell Biol. 2015; 16 (4): 221-31. doi: 10.1038/nrm3958. PubMed PMID: 25735911; PubMed Central PMCID: PMCPMC4494666.
[3] Rapoport TA. Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature. 2007; 450 (7170): 663-9. doi: 10.1038/nature06384. PubMed PMID: 18046402.
[4] Lazar C, Uta M, Branza-Nichita N. Modulation of the unfolded protein response by the human hepatitis B virus. Front Microbiol. 2014; 5: 433. doi: 10.3389/fmicb.2014.00433. PubMed PMID: 25191311; PubMed Central PMCID: PMCPMC4137222.
[5] Lee J, Ozcan U. Unfolded protein response signaling and metabolic diseases. J Biol Chem. 2014; 289 (3): 1203-11. doi: 10.1074/jbc.R113.534743. PubMed PMID: 24324257; PubMed Central PMCID: PMCPMC3894306.
[6] Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011; 334 (6059): 1081-6. doi: 10.1126/science.1209038. PubMed PMID: 22116877.
[7] Rath E, Haller D. Inflammation and cellular stress: a mechanistic link between immune-mediated and metabolically driven pathologies. Eur J Nutr. 2011; 50 (4): 219-33. doi: 10.1007/s00394-011-0197-0. PubMed PMID: 21547407.
[8] Zhang K. Integration of ER stress, oxidative stress and the inflammatory response in health and disease. Int J Clin Exp Med. 2010; 3 (1): 33-40. PubMed PMID: 20369038; PubMed Central PMCID: PMCPMC2848304.
[9] Kitamura M. Control of NF-kappaB and inflammation by the unfolded protein response. Int Rev Immunol. 2011; 30 (1): 4-15. doi: 10.3109/08830185.2010.522281. PubMed PMID: 21235322.
[10] Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010; 140 (6): 900-17. doi: 10.1016/j.cell.2010.02.034. PubMed PMID: 20303879; PubMed Central PMCID: PMCPMC2887297.
[11] Zhang K, Shen X, Wu J, Sakaki K, Saunders T, Rutkowski DT, et al. Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell. 2006; 124 (3): 587-99. doi: 10.1016/j.cell.2005.11.040. PubMed PMID: 16469704.
[12] Gotoh T, Endo M, Oike Y. Endoplasmic reticulum stress-related inflammation and cardiovascular diseases. Int J Inflam. 2011; 2011: 259462. doi: 10.4061/2011/259462. PubMed PMID: 21755026; PubMed Central PMCID: PMCPMC3132612.
[13] Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008; 454 (7203): 455-62. doi: 10.1038/nature07203. PubMed PMID: 18650916; PubMed Central PMCID: PMCPMC2727659.
[14] Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007; 8 (7): 519-29. doi: 10.1038/nrm2199. PubMed PMID: 17565364.
[15] Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science. 2000; 287 (5453): 664-6. PubMed PMID: 10650002.
[16] Perri ER, Thomas CJ, Parakh S, Spencer DM, Atkin JD. The Unfolded Protein Response and the Role of Protein Disulfide Isomerase in Neurodegeneration. Front Cell Dev Biol. 2015; 3: 80. doi: 10.3389/fcell.2015.00080. PubMed PMID: 26779479; PubMed Central PMCID: PMCPMC4705227.
[17] Grootjans J, Kaser A, Kaufman RJ, Blumberg RS. The unfolded protein response in immunity and inflammation. Nat Rev Immunol. 2016; 16 (8): 469-84. doi: 10.1038/nri.2016.62. PubMed PMID: 27346803; PubMed Central PMCID: PMCPMC5310224.
[18] Hill JC, Maske R. Pathogenesis of pterygium. Eye (Lond). 1989; 3 (Pt 2): 218-26. doi: 10.1038/eye.1989.31. PubMed PMID: 2695353.
[19] Hilgers JH. Pterygium: its incidence, heredity and etiology. Am J Ophthalmol. 1960; 50: 635-44. PubMed PMID: 13714249.
[20] Detels R, Dhir SP. Pterygium: a geographical study. Arch Ophthalmol. 1967; 78 (4): 485-91. PubMed PMID: 6046844.
[21] Kheirkhah A, Casas V, Sheha H, Raju VK, Tseng SC. Role of conjunctival inflammation in surgical outcome after amniotic membrane transplantation with or without fibrin glue for pterygium. Cornea. 2008; 27 (1): 56-63. doi: 10.1097/ICO.0b013e31815873da. PubMed PMID: 18245968.
[22] Halliday M, Mallucci GR. Targeting the unfolded protein response in neurodegeneration: A new approach to therapy. Neuropharmacology. 2014; 76 Pt A: 169-74. doi: 10.1016/j.neuropharm.2013.08.034. PubMed PMID: 24035917.
[23] Kaufman RJ. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 1999; 13 (10): 1211-33. PubMed PMID: 10346810.
[24] Sherman MY, Goldberg AL. Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron. 2001; 29 (1): 15-32. PubMed PMID: 11182078.
[25] Ali MM, Bagratuni T, Davenport EL, Nowak PR, Silva-Santisteban MC, Hardcastle A, et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 2011; 30 (5): 894-905. doi: 10.1038/emboj.2011.18. PubMed PMID: 21317875; PubMed Central PMCID: PMCPMC3049214.
[26] Chen Y, Brandizzi F. IRE1: ER stress sensor and cell fate executor. Trends Cell Biol. 2013; 23 (11): 547-55. doi: 10.1016/j.tcb.2013.06.005. PubMed PMID: 23880584; PubMed Central PMCID: PMCPMC3818365.
[27] Maurel M, Chevet E, Tavernier J, Gerlo S. Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem Sci. 2014; 39 (5): 245-54. doi: 10.1016/j.tibs.2014.02.008. PubMed PMID: 24657016.
[28] Lee AH, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol. 2003; 23 (21): 7448-59. PubMed PMID: 14559994; PubMed Central PMCID: PMCPMC207643.
[29] Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell. 2000; 6 (6): 1355-64. PubMed PMID: 11163209.
[30] Glembotski CC. Roles for ATF6 and the sarco/endoplasmic reticulum protein quality control system in the heart. J Mol Cell Cardiol. 2014; 71: 11-5. doi: 10.1016/j.yjmcc.2013.09.018. PubMed PMID: 24140798; PubMed Central PMCID: PMCPMC4157898.
[31] Yamazaki H, Hiramatsu N, Hayakawa K, Tagawa Y, Okamura M, Ogata R, et al. Activation of the Akt-NF-kappaB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J Immunol. 2009; 183 (2): 1480-7. doi: 10.4049/jimmunol.0900017. PubMed PMID: 19561103; PubMed Central PMCID: PMCPMC2762936.
[32] Hu P, Han Z, Couvillon AD, Kaufman RJ, Exton JH. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol Cell Biol. 2006; 26 (8): 3071-84. doi: 10.1128/MCB.26.8.3071-3084.2006. PubMed PMID: 16581782; PubMed Central PMCID: PMCPMC1446932.
[33] Mei Y, Thompson MD, Cohen RA, Tong X. Endoplasmic Reticulum Stress and Related Pathological Processes. J Pharmacol Biomed Anal. 2013; 1 (2): 1000107. PubMed PMID: 24611136; PubMed Central PMCID: PMCPMC3942890.
Cite This Article
  • APA Style

    Sheng Zhou, Jing Yang. (2019). Involvement of ER Stress in Human Primary Pterygium. International Journal of Ophthalmology & Visual Science, 4(2), 30-36. https://doi.org/10.11648/j.ijovs.20190402.11

    Copy | Download

    ACS Style

    Sheng Zhou; Jing Yang. Involvement of ER Stress in Human Primary Pterygium. Int. J. Ophthalmol. Vis. Sci. 2019, 4(2), 30-36. doi: 10.11648/j.ijovs.20190402.11

    Copy | Download

    AMA Style

    Sheng Zhou, Jing Yang. Involvement of ER Stress in Human Primary Pterygium. Int J Ophthalmol Vis Sci. 2019;4(2):30-36. doi: 10.11648/j.ijovs.20190402.11

    Copy | Download

  • @article{10.11648/j.ijovs.20190402.11,
      author = {Sheng Zhou and Jing Yang},
      title = {Involvement of ER Stress in Human Primary Pterygium},
      journal = {International Journal of Ophthalmology & Visual Science},
      volume = {4},
      number = {2},
      pages = {30-36},
      doi = {10.11648/j.ijovs.20190402.11},
      url = {https://doi.org/10.11648/j.ijovs.20190402.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijovs.20190402.11},
      abstract = {Purpose: The aim of this study was to investigate the ER stress activation in human primary pterygium. Methods and materials: Human primary pterygium or normal Tenon's capsule tissues were obtained from patients with primary pterygium following surgical excision or from normal human fresh cadaver eyes. The tissues were processed within 2 hours. The mRNA or protein specimens were extracted from those tissues for analysis, cryosections of those tissues were prepared for immunohistochemical staining. The mRNA levels of endoplasmic reticulum (ER) stress-related factors in those tissues were detected by qPCR analysis and the related proteins levels were detected by qPCR analysis and immunohistochemical staining or western blotting. Results: The ER stress-related gene transcription levels of GRP78,spliced XBP-1, ATF4 and ATF6 and the protein expression levels of GRP78, p-IRE1α, p-eIF2α and ATF6 were all increased in the human primary pterygium tissues when compared with the normal control tissues. Conclusion: The results in this study suggest that the three unfolded protein response pathways are all activated in the human primary pterygium tissues, which indicates that the ER stress is involved in the progression of pterygium, and also suggests a potential mechanism of ER stress-induced inflammation in the human primary pterygium tissues.},
     year = {2019}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Involvement of ER Stress in Human Primary Pterygium
    AU  - Sheng Zhou
    AU  - Jing Yang
    Y1  - 2019/07/11
    PY  - 2019
    N1  - https://doi.org/10.11648/j.ijovs.20190402.11
    DO  - 10.11648/j.ijovs.20190402.11
    T2  - International Journal of Ophthalmology & Visual Science
    JF  - International Journal of Ophthalmology & Visual Science
    JO  - International Journal of Ophthalmology & Visual Science
    SP  - 30
    EP  - 36
    PB  - Science Publishing Group
    SN  - 2637-3858
    UR  - https://doi.org/10.11648/j.ijovs.20190402.11
    AB  - Purpose: The aim of this study was to investigate the ER stress activation in human primary pterygium. Methods and materials: Human primary pterygium or normal Tenon's capsule tissues were obtained from patients with primary pterygium following surgical excision or from normal human fresh cadaver eyes. The tissues were processed within 2 hours. The mRNA or protein specimens were extracted from those tissues for analysis, cryosections of those tissues were prepared for immunohistochemical staining. The mRNA levels of endoplasmic reticulum (ER) stress-related factors in those tissues were detected by qPCR analysis and the related proteins levels were detected by qPCR analysis and immunohistochemical staining or western blotting. Results: The ER stress-related gene transcription levels of GRP78,spliced XBP-1, ATF4 and ATF6 and the protein expression levels of GRP78, p-IRE1α, p-eIF2α and ATF6 were all increased in the human primary pterygium tissues when compared with the normal control tissues. Conclusion: The results in this study suggest that the three unfolded protein response pathways are all activated in the human primary pterygium tissues, which indicates that the ER stress is involved in the progression of pterygium, and also suggests a potential mechanism of ER stress-induced inflammation in the human primary pterygium tissues.
    VL  - 4
    IS  - 2
    ER  - 

    Copy | Download

Author Information
  • State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

  • State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

  • Sections