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Transcriptional and epigenetic effects of Vitis vinifera L. leaf extract on UV-stressed human dermal fibroblasts

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A Correction to this article was published on 15 June 2023

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Abstract

Adverse environmental conditions such as UV radiation induce oxidative and aging events leading to severe damage to human skin cells. Natural products such as plant extracts have been implicated in the skin anti-oxidant and anti-aging cellular protection against environmental stress. Moreover, environmental factors have been shown to impact chromatin structure leading to altered gene expression programs with profound changes in cellular functions. In this study, we assessed the in vitro effect of a leaf extract from Vitis vinifera L. on UV-stressed primary human dermal fibroblasts, focusing on gene expression and DNA methylation as an epigenetic factor. Expression analysis of two genes known to be implicated in skin anti-aging, SIRT1and HSP4, demonstrated significant induction in the presence of the extract under normal or UVA conditions. In addition, DNA methylation profiling of SIRT1 and HSP47 promoters showed that the V. vinifera L. extract induced changes in the DNA methylation pattern of both genes that may be associated with SIRT1 and HSP47 gene expression. Our study shows for the first time transcriptional and DNA methylation alterations on human skin fibroblasts exposed to UV stress and suggest a protective effect of a V. vinifera extract possibly through transcriptional regulation of critical skin anti-aging genes.

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References

  1. Yamaba H, Haba M, Kunita M et al (2016) Morphological change of skin fibroblasts induced by UV irradiation is involved in photoaging. Exp Dermatol 25:45–51. https://doi.org/10.1111/exd.13084

    Article  CAS  PubMed  Google Scholar 

  2. Varani J, Schuger L, Dame MK et al (2004) Reduced fibroblast interaction with intact collagen as a mechanism for depressed collagen synthesis in photodamaged skin. J Invest Dermatol 122:1471–1479. https://doi.org/10.1111/j.0022-202X.2004.22614.x

    Article  CAS  PubMed  Google Scholar 

  3. Amaro-Ortiz A, Yan B, D’Orazio J (2014) Ultraviolet radiation, aging and the skin: prevention of damage by topical cAMP manipulation. Molecules 19:6202–6219. https://doi.org/10.3390/molecules19056202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Soto M, Falqué E, Domínguez H (2015) Relevance of natural phenolics from grape and derivative products in the formulation of cosmetics. Cosmetics 2:259–276. https://doi.org/10.3390/cosmetics2030259

    Article  CAS  Google Scholar 

  5. Alcendor RR, Gao S, Zhai P et al (2007) Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 100:1512–1521. https://doi.org/10.1161/01.RES.0000267723.65696.4a

    Article  CAS  PubMed  Google Scholar 

  6. Haigis MC, Guarente LP (2006) Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction. Genes Dev 20:2913–2921. https://doi.org/10.1101/gad.1467506

    Article  CAS  PubMed  Google Scholar 

  7. Guarente L, Picard F (2005) Calorie restriction—the SIR2 connection. Cell 120:473–482. https://doi.org/10.1016/j.cell.2005.01.029

    Article  CAS  PubMed  Google Scholar 

  8. Ito S, Nagata K (2017) Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone. Semin Cell Dev Biol 62:142–151. https://doi.org/10.1016/j.semcdb.2016.11.005

    Article  CAS  PubMed  Google Scholar 

  9. Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403:795–800. https://doi.org/10.1038/35001622

    Article  CAS  PubMed  Google Scholar 

  10. Pal S, Tyler JK (2016) Epigenetics and aging. Sci Adv 2:e1600584. https://doi.org/10.1126/sciadv.1600584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liang YC, Widelitz RCC (2018) Epigenetic regulation of skin development and regeneration. Springer, Cham

  12. Pagiatakis C, Musolino E, Gornati R et al (2019) Epigenetics of aging and disease: a brief overview. Aging Clin Exp Res. https://doi.org/10.1007/s40520-019-01430-0

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lantzouraki DZ, Tsiaka T, Soteriou N et al (2020) Antioxidant profiles of Vitis vinifera L. and Salvia triloba L. leaves using high-energy extraction methodologies. J AOAC Int 103:413–421. https://doi.org/10.5740/jaoacint.19-0261

    Article  PubMed  Google Scholar 

  14. Hoffmann M, Wu Y-J, Gerber M et al (2010) Fusion-active glycoprotein G mediates the cytotoxicity of vesicular stomatitis virus M mutants lacking host shut-off activity. J Gen Virol 91:2782–2793. https://doi.org/10.1099/vir.0.023978-0

    Article  CAS  PubMed  Google Scholar 

  15. Chen H, Li Y, Tollefsbol TO (2013) Cell senescence culturing methods. Methods Mol Biol. 21:1–10

    Google Scholar 

  16. Letsiou S, Kalliampakou K, Gardikis K et al (2017) Skin protective effects of nannochloropsis gaditana extract on H2O2-stressed human dermal fibroblasts. Front Mar Sci 4. https://doi.org/10.3389/fmars.2017.00221

  17. Ramakers C, Ruijter JM, Deprez RHL, Moorman AF (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 339:62–66. https://doi.org/10.1016/S0304-3940(02)01423-4

    Article  CAS  PubMed  Google Scholar 

  18. Beier V, Mund C, Hoheisel JD (2006) Monitoring methylation changes in cancer. In: Analytics of protein–DNA interactions. Springer, Berlin, pp 1–11

  19. Zhao L, Cao J, Hu K, He X, Yun D, Tong T, Han L (2020) Sirtuins and their biological relevance in aging and age-related diseases. Aging Dis 11. https://doi.org/10.14336/AD.2019.0820

  20. Crouch SPM, Kozlowski R, Slater KJ, Fletcher J (1993) The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity. J Immunol Methods 160:81–88. https://doi.org/10.1016/0022-1759(93)90011-U

    Article  CAS  PubMed  Google Scholar 

  21. Deters AM, Schröder KR, Hensel A (2005) Kiwi fruit (Actinidia chinensis L.) polysaccharides exert stimulating effects on cell proliferation via enhanced growth factor receptors, energy production, and collagen synthesis of human keratinocytes, fibroblasts, and skin equivalents. J Cell Physiol 202:717–722. https://doi.org/10.1002/jcp.20161

    Article  CAS  PubMed  Google Scholar 

  22. Yamakuchi M (2012) MicroRNA regulation of SIRT1. Front Physiol 3. https://doi.org/10.3389/fphys.2012.00068

  23. Elibol B, Kilic U (2018) High levels of SIRT1 expression as a protective mechanism against disease-related conditions. Front Endocrinol (Lausanne) 9. https://doi.org/10.3389/fendo.2018.00614

  24. Kabra N, Li Z, Chen L et al (2009) SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem 284:18210–18217. https://doi.org/10.1074/jbc.M109.000034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Satoh A, Stein L, Imai S (2011) The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Handb Exp Pharmocol 206:125–162

    Article  CAS  Google Scholar 

  26. Hubbard BP, Sinclair DA (2014) Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci 35:146–154. https://doi.org/10.1016/j.tips.2013.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang C, Wen C, Lin J, Shen G (2015) Protective effect of pyrroloquinoline quinine on ultraviolet a irradiation-induced human dermal fibroblast senescence in vitro proceeds via the anti-apoptotic sirtuin 1/nuclear factor-derived erythroid 2-related factor 2/heme oxygenase 1 pathway. Mol Med Rep 12:4382–4388. https://doi.org/10.3892/mmr.2015.3990

    Article  CAS  PubMed  Google Scholar 

  28. Khan ES, Sankaran S, Paez JI et al (2019) Photoactivatable hsp47: a tool to regulate collagen secretion and assembly. Adv Sci 6:1801982. https://doi.org/10.1002/advs.201801982

    Article  CAS  Google Scholar 

  29. He W, Dai C (2015) Key fibrogenic signaling. Curr Pathobiol Rep 3(183):192. https://doi.org/10.1007/s40139-015-0077-z

    Article  Google Scholar 

  30. Makareeva E, Leikin S (2007) Procollagen triple helix assembly: an unconventional chaperone-assisted folding paradigm. PLoS ONE 2:e1029. https://doi.org/10.1371/journal.pone.0001029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nizard C, Noblesse E, Boisdé C et al (2004) Heat shock protein 47 expression in aged normal human fibroblasts: modulation by salix alba extract. Ann N Y Acad Sci 1019:223–227. https://doi.org/10.1196/annals.1297.037

    Article  PubMed  Google Scholar 

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Contributions

SL conceived, planned and oversaw the experiments. SL carried out the experiments on the RT-qPCR analysis, AK carried out experiments on epigenetics analysis. SL and AK analyzed and integrated the datasets and drafted the manuscript. AT critically read and contributed to improve the MS. K.G. made extract preparations K.G. critically read and contributed to improve the MS. E.S. made extract preparations and optimization and collected the plant material.

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Correspondence to Sophia Letsiou.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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The original online version of this article was revised: The authors "Eleni Spanidi" and "Konstantinos Gardikis" are included as 4th and 5th authors. The sections "Materials and methods, Discussions, Author contributions and funding" are updated.

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Letsiou, S., Kapazoglou, A., Tsaftaris, A. et al. Transcriptional and epigenetic effects of Vitis vinifera L. leaf extract on UV-stressed human dermal fibroblasts. Mol Biol Rep 47, 5763–5772 (2020). https://doi.org/10.1007/s11033-020-05645-7

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