Abstract
Exposure to sunlight, mainly UVA, leads to typical changes in the features of the skin known as photoaging. UVA irradiation induces the expression of proteases that are responsible for the degradation of the extracellular matrix proteins to results in photoaging; it also downregulates the expression of proteins that are needed for the skin structure. Since, it is known that cells in the neighborhood of irradiated cells, but not directly exposed to it, often manifest responses like their irradiated counterparts, it is important to evaluate if these bystander cells too, can contribute to photoaging. UVA induced cell cycle arrest has been associated with photoaging, from flow cytometry analysis we found that there was an induction of cell cycle arrest at the G1/S phase in the UVA-bystander cells. The expression of some key photoaging marker genes likes, matrix metalloproteinases (MMP-1, MMP-3, MMP-9), cyclooxygenase-2 (COX-2), collagen1 and elastin were assessed from qRT-PCR. Up-regulation of MMP-1 and COX-2, downregulation of collagen1 and elastin, along with suppression below normal expression for MMP-3 and MMP-9 was observed in the UVA-bystander A375 cells. Our findings suggest that UVA-bystander cells may contribute to the process of photoaging.
Highlights
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G1/S cell cycle arrest was observed in UVA-bystander A375 cells.
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The expression of MMP-1 & COX-2 was upregulated in UVA-bystander A375 cells.
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Collagen 1 & elastin expression was also downregulated in these bystander cells.
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Expression of MMP-3 & -9 in the UVA-bystander cells lower than that in control cells.
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References
Quan, T., Qin, Z., Xia, W., Shao, Y., Voorhees, J. J., & Fisher, G. J. (2009). Matrix-degrading metalloproteinases in photoaging. Journal of Investigative Dermatology Symposium Proceedings, 14, 20–24. https://doi.org/10.1038/jidsymp.2009.8.
Ghosh, R. (2017). Role of proteases in photo-aging of the skin. In S. Chakraborti & N. S. Dhalla (Eds.), Proteases in Physiology and Pathology (pp. 435–449). Singapore: Springer. https://doi.org/10.1007/978-981-10-2513-6_20.
Pittayapruek, P., Meephansan, J., Prapapan, O., Komine, M., & Ohtsuki, M. (2016). Role of matrix metalloproteinases in Photoaging and photocarcinogenesis. International Journal of Molecular Sciences, 17, 1–20. https://doi.org/10.3390/ijms17060868.
Chauhan, P., & Shakya, M. (2009). Modeling signaling pathways leading to wrinkle formation: identification of the skin aging target. Indian Journal of Dermatology, Venereology and Leprology, 75, 463–468. https://doi.org/10.4103/0378-6323.55388.
Habib, M. A., Salem, S. A. M., Hakim, S. A., & Shalan, Y. A. M. (2014). Comparative immunohistochemical assessment of cutaneous cyclooxygenase-2 enzyme expression in chronological aging and photoaging. Photodermatology, Photoimmunology and Photomedicine, 30, 43–51. https://doi.org/10.1111/phpp.12087.
Widel, M. (2012). Bystander effect induced by UV radiation; why should we be interested?. Advances in Hygiene & Experimental Medicine (Online), 66, 828–837. https://doi.org/10.5604/17322693.1019532.
Schorpp, M., Mallick, U., Rahmsdorf, H. J., & Herrlich, P. (1984). UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells. Cell, 37, 861–868. https://doi.org/10.1016/0092-8674(84)90421-5.
Rotem, N. A., Axelrod, J. H., & Miskin, R. U. (1987). Induction of urokinase-type plasminogen activator by UV light in human fetal fibroblasts is mediated through a UV-induced secreted protein. Molecular and Cellular Biology, 7, 622–631. https://doi.org/10.1016/S0021-9258(18)53311-1.
Krämer, M., Sachsenmaier, C., Herrlich, P., & Rahmsdorf, H. J. (1993). UV irradiation-induced interleukin-1 and basic fibroblast growth factor synthesis and release mediate part of the UV response. Journal of Biological Chemistry, 268, 6734–6741. https://doi.org/10.1016/S0021-9258(18)53311-1.
Bender, K., Blattner, C., Knebel, A., Iordanov, M., Herrlich, P., & Rahmsdorf, H. J. (1997). UV-induced signal transduction. Journal of Photochemistry and Photobiology B: Biology, 37, 1–17. https://doi.org/10.1016/S1011-1344(96)07459-3.
Kulms, D., & Schwarz, T. (2000). Molecular mechanisms of UV‐induced apoptosis. Photodermatology, Photoimmunology and Photomedicine, 16, 195–201. https://doi.org/10.1034/j.1600-0781.2000.160501.x.
Peng, Y., Zhang, M., Zheng, L., Liang, Q., Li, H., Chen, J. T., Guo, H., Yoshina, S., Chen, Y. Z., Zhao, X., & Wu, X. (2017). Cysteine protease cathepsin B mediates radiation-induced bystander effects. Nature, 547, 458–462. https://doi.org/10.1038/nature23284.
Lin, X., Wei, F., Major, P., Al-Nedawi, K., Al Saleh, H. A., & Tang, D. (2017). Microvesicles contribute to the bystander effect of DNA damage. International Journal of Molecular Sciences, 18, 788 https://doi.org/10.3390/ijms18040788.
Le, M., Fernandez-Palomo, C., McNeill, F. E., Seymour, C. B., Rainbow, A. J., & Mothersill, C. E. (2017). Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: reconciling the mechanisms mediating the bystander effect. PloS one, 12, e0173685 https://doi.org/10.1371/journal.pone.0173685.
Hu, W., Xu, S., Yao, B., Hong, M., Wu, X., Pei, H., Chang, L., Ding, N., Gao, X., Ye, C., & Wang, J. (2014). MiR-663 inhibits radiation-induced bystander effects by targeting TGFB1 in a feedback mode. RNA Biology, 11, 1189–1198. https://doi.org/10.4161/rna.34345.
Ghosh, R., & Bhaumik, G. (1995). Supernatant medium from UV-irradiated cells influences the cytotoxicity and mutagenicity of V79 cells. Mutation Research/Environmental Mutagenesis and Related Subjects, 335, 129–135. https://doi.org/10.1016/0165-1161(95)00011-9.
Hansda, S., Ghosh, G., & Ghosh, R. (2020). 9-phenyl acridine photosensitizes A375 cells to UVA radiation. Heliyon, 6, e04733 https://doi.org/10.1016/j.heliyon.2020.e04733.
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 25, 402–408. https://doi.org/10.1006/meth.2001.1262.
Deng, M., Xu, Y., Yu, Z., Wang, X., Cai, Y., Zheng, H., Li, W., & Zhang, W. (2019). Protective effect of fat extract on UVB-induced photoaging in vitro and in vivo. Oxidative Medicine and Cellular Longevity, 2019, 1–11. https://doi.org/10.1155/2019/6146942.
Wlaschek, M., Tantcheva-Poór, I., Naderi, L., Ma, W., Schneider, L. A., Razi-Wolf, Z., Schüller, J., & Scharffetter-Kochanek, K. (2001). Solar UV irradiation and dermal photoaging. Journal of Photochemistry and Photobiology B: Biology, 63, 41–51. https://doi.org/10.1016/S1011-1344(01)00201-9.
Ghosh, R., Guha, D., Bhowmik, S., & Karmakar, S. (2013). Antioxidant enzymes and the mechanism of the bystander effect induced by ultraviolet C irradiation of A375 human melanoma cells. Mutation Research Genetic Toxicology and Environmental Mutagenesis, 757, 83–90. https://doi.org/10.1016/j.mrgentox.2013.06.022.
Mao, Z., Ke, Z., Gorbunova, V., & Seluanov, A. (2012). Replicatively senescent cells are arrested in G1 and G2 phases. Aging, 4, 431–435. https://doi.org/10.18632/aging.100467.
Petit‐frère, C., Clingen, P. H., Grewe, M., Krutmann, J., Roza, L., Arlett, C. F., & Green, M. H. (1998). Induction of interleukin‐6 production by ultraviolet radiation in normal human epidermal keratinocytes and in a human keratinocyte cell line is mediated by DNA damage. Journal of Investigative Dermatology, 111, 354–358. https://doi.org/10.1038/sj.jid.5602962.
Schneider, L. A., Raizner, K., Wlaschek, M., Brenneisen, P., Gethöffer, K., & Scharffetter‐Kochanek, K. (2017). UVA‐1 exposure in vivo leads to an IL‐6 surge within the skin. Experimental Dermatology, 26, 830–832. https://doi.org/10.1111/exd.13286.
Wlaschek, M., Bolsen, K., Herrmann, G., Schwarz, A., Wilmroth, F., Heinrich, P. C., Goerz, G., & Scharffetter-Kochanek, K. (1993). UVA-induced autocrine stimulation of fibroblast-derived-collagenase by IL-6: a possible mechanism in dermal photodamage? Journal of Investigative Dermatology, 101, 164–168. https://doi.org/10.1111/1523-1747.ep12363644.
Wlaschek, M., Heinen, G., Poswig, A., Schwarz, A., Krieg, T., & Scharffetter‐Kochanek, K. (1994). UVA‐induced autocrine stimulation of fibroblast‐derived collagenase/mmp‐1 by interrelated loops of interleukin–1 and interleukin–6. Photochemistry and Photobiology, 59, 550–556. https://doi.org/10.1111/j.1751-1097.1994.tb02982.x.
Buechner, N., Schroeder, P., Jakob, S., Kunze, K., Maresch, T., Calles, C., Krutmann, J., & Haendeler, J. (2008). Changes of MMP-1 and collagen type Iα1 by UVA, UVB and IRA are differentially regulated by Trx-1. Experimental Gerontology, 43, 633–637. https://doi.org/10.1016/j.exger.2008.04.009.
Quan, T., Little, E., Quan, H., Qin, Z., Voorhees, J. J., & Fisher, G. J. (2013). Elevated matrix metalloproteinases and collagen fragmentation in photodamaged human skin: Impact of altered extracellular matrix microenvironment on dermal fibroblast function. Journal of Investigative Dermatology, 133, 1362–1366. https://doi.org/10.1038/jid.2012.509.
Wen, K. C., Fan, P. C., Tsai, S. Y., Shih, I. C., & Chiang, H. M. (2012). Ixora parviflora protects against UVB-induced photoaging by inhibiting the expression of MMPs, MAP kinases, and COX-2 and by promoting type I procollagen synthesis. Evidence-Based Complementary and Alternative Medicine, 2012, 1–11. https://doi.org/10.1155/2012/417346.
Steinbrenner, H., Ramos, M. C., Stuhlmann, D., Sies, H., & Brenneisen, P. (2003). UVA-mediated downregulation of MMP-2 and MMP-9 in human epidermal keratinocytes. Biochemical and Biophysical Research Communications, 308, 486–491. https://doi.org/10.1016/S0006-291X(03)01430-X.
Tanaka, K., Asamitsu, K., Uranishi, H., Iddamalgoda, A., Ito, K., Kojima, H., & Okamoto, T. (2010). Protecting skin photoaging by NF-κB inhibitor. Current Drug Metabolism, 11, 431–435. https://doi.org/10.2174/138920010791526051.
Jean, C., Bogdanowicz, P., Haure, M. J., Castex-Rizzi, N., Fournié, J. J., & Laurent, G. (2011). UVA-activated synthesis of metalloproteinases 1, 3 and 9 is prevented by a broad-spectrum sunscreen. Photodermatology, Photoimmunology and Photomedicine, 27, 318–324. https://doi.org/10.1111/j.1600-0781.2011.00627.x.
Ghosh, R., Guha, D., Bhowmik, S., & Karmakar, S. (2012). Some UV-bystander effects are mediated through induction of antioxidant defense in mammalian cells. Indian Journal of Biochemistry and Biophysics, 49, 371–378. http://nopr.niscair.res.in/handle/123456789/14837
Reunanen, N., & VeliMatti, K. (2013). Matrix metalloproteinases in cancer cell invasion. In Madame Curie Bioscience Database [Internet] (pp. 1–19). Austin, TX, USA: Landes Bioscience. https://www.ncbi.nlm.nih.gov/books/NBK6598/.
Winer, A., Adams, S., & Mignatti, P. (2018). Matrix metalloproteinase inhibitors in cancer therapy: Turning past failures into future successes. Molecular Cancer Therapeutics, 17, 1147–1155. https://doi.org/10.1158/1535-7163.MCT-17-0646.
Hansda, S., & Ghosh, R. (2021). Bystander effect of ultraviolet A radiation protects A375 melanoma cells by induction of antioxidant defense. Journal of Environmental Science and Health, Part C, 1–22. https://doi.org/10.1080/26896583.2021.1994820
Prasanth, M. I., Gayathri, S., Bhaskar, J. P., Krishnan, V., & Balamurugan, K. (2020). Understanding the role of p38 and JNK mediated MAPK pathway in response to UV-A induced photoaging in Caenorhabditis elegans. Journal of Photochemistry and Photobiology B Biology, 205, 1–7. https://doi.org/10.1016/j.jphotobiol.2020.111844.
Shin, E. J., Lee, J. S., Hong, S., Lim, T. G., & Byun, S. (2019). Quercetin directly targets JAK2 and PKCδ and prevents UV-induced photoaging in human skin. International Journal of Molecular Sciences, 20, 5262 https://doi.org/10.3390/ijms20215262.
Kwon, K. R., Alam, M. B., Park, J. H., Kim, T. H., & Lee, S. H. (2019). Attenuation of UVB-induced photo-aging by polyphenolic-rich Spatholobus suberectus stem extract via modulation of MAPK/AP-1/MMPs signaling in human keratinocytes. Nutrients, 11, 1341 https://doi.org/10.3390/nu11061341.
Eftekhari-Kenzerki, Z., Fardid, R., & Behzad-Behbahani, A. (2019). Impact of silver nanoparticles on the ultraviolet radiation direct and bystander effects on TK6 cell line. Journal of Medical Physics, 44, 118 https://doi.org/10.4103/jmp.JMP_111_18.
Bachelor, M. A., & Bowden, G. T. (2004). UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression. Seminars in Cancer Biology, 14, 131–138. https://doi.org/10.1016/j.semcancer.2003.09.017.
Shabunin, A. S., Yudin, V. E., Dobrovolskaya, I. P., Zinovyev, E. V., Zubov, V., Ivan’kova, E. M., & Morganti, P. (2019). Composite wound dressing based on chitin/chitosan nanofibers: processing and biomedical applications. Cosmetics, 6, 16 https://doi.org/10.3390/cosmetics6010016.
Lee, M. E., Kim, S. R., Lee, S., Jung, Y. J., Choi, S. S., Kim, W. J., & Han, J. A. (2012). Cyclooxygenase-2 inhibitors modulate skin aging in a catalytic activity-independent manner. Experimental and Molecular Medicine, 44, 536–544. https://doi.org/10.3858/emm.2012.44.9.061.
Weihermann, A. C., Lorencini, M., Brohem, C. A., & de Carvalho, C. M. (2017). Elastin structure and its involvement in skin photoageing. International Journal of Cosmetic Science, 39, 241–247. https://doi.org/10.1111/ics.12372.
Acknowledgements
The authors acknowledge the infrastructural facility from the University of Kalyani (K.U.), DST-PURSE and UGC-SAP, Govt. of India. Thanks are due to Dr. Utpal Basu, K.U., for allowing use of some laboratory facilities.
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Hansda, S., Ghosh, G. & Ghosh, R. The Role of Bystander Effect in Ultraviolet A Induced Photoaging. Cell Biochem Biophys 80, 657–664 (2022). https://doi.org/10.1007/s12013-022-01099-9
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DOI: https://doi.org/10.1007/s12013-022-01099-9