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Chloroform induces cystein-rich 61, a mediator of collagen homeostasis via early growth response-1 dependent pathway in human skin dermal fibroblasts

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Abstract

Volatile organic compounds (VOCs) are major air pollutants known to have adverse effects on skin. Many reports have shown an association between air pollutants and skin aging. However, there is no report on VOCs association with skin aging. The aim of this study is to identify the biologic effects of VOCs on fibroblasts. We investigated the effects of chloroform on cysteine-rich 61 (CYR61) expression in human skin fibroblasts using western blot and reverse transcriptionpolymerase chain reaction. We also observed the change of type I procollagen and matrix metalloproteinase after exposure to chloroform using western blot. We explored the involvement of early growth response-1 (Egr-1) using siRNA s in the fibroblasts. Chloroform exposure increased the expression of CYR61 protein and mRNA level. Elevated CYR61 downregulates type I procollagen and upregulates MMP-1. Egr-1 overexpression upregulates CYR61 promoter activity. CYR61 promoter activity was lower in Egr-1 siRNA-transfected fibroblasts. The present study demonstrates that CYR61 is transcriptionally regulated by chloroform exposure through transcription factor Egr-1, and alters collagen homeostasis in human skin fibroblasts.

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References

  1. Lademann, J. et al. Penetration of microparticles into human skin. Hautarzt 55:1117–1119 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Rittié, L. & Fisher, G. J. UV-light-induced signal cascades and skin aging. Ageing Res Rev 1:705–720 (2002).

    Article  PubMed  Google Scholar 

  3. Schroeder, P., Schieke, S. & Morita, A. Premature Skin Aging by Infrared Radiation, Tobacco Smoke and Ozone, in Skin Aging (eds. Gilchrest, B. & Krutmann, J.) 45–53 (Springer Berlin Heidelberg, 2006).

    Chapter  Google Scholar 

  4. Vierkötter, A. et al. Airborne particle exposure and extrinsic skin aging. J Invest Dermatol 130:2719–2726 (2010).

    Article  PubMed  Google Scholar 

  5. Huss-Marp, J. et al. Influence of short-term exposure to airborne Der p 1 and volatile organic compounds on skin barrier function and dermal blood flow in patients with atopic eczema and healthy individuals. Clin Exp Allergy 36:338–345 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Yeger, H. & Perbal, B. The CCN family of genes: a perspective on CCN biology and therapeutic potential. J Cell Commun Signal 1:159–164 (2007).

    Article  PubMed  Google Scholar 

  7. Chen, C. C., Mo, F. E. & Lau, L. F. The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts. J Biol Chem 276: 47329–47337 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Kireeva, M. L., Mo, F. E., Yang, G. P. & Lau, L. F. Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion. Mol Cell Biol 16:1326–1334 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Perbal, B., Brigstock, D. R. & Lau, L. F. Report on the second international workshop on the CCN family of genes. Mol Path 56:80–85 (2003).

    Article  CAS  Google Scholar 

  10. Quan, T. et al. Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin. Am J Pathol 169:482–490 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Khachigian, L. M. & Collins, T. Early growth response factor 1: a pleiotropic mediator of inducible gene expression. J Mol Med (Berl) 76:613–616 (1998).

    Article  CAS  Google Scholar 

  12. McMahon, S. B. & Monroe, J. G. The role of early growth response gene 1 (egr-1) in regulation of the immune response. J Leukoc Biol 60:159–166 (1996).

    CAS  PubMed  Google Scholar 

  13. Grote, K. et al. Stretch-inducible expression of the angiogenic factor CCN1 in vascular smooth muscle cells is mediated by Egr-1. J Biol Chem 279:55675–55681 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Baudouin, C., Charveron, M., Tarroux, R. & Gall, Y. Environmental pollutants and skin cancer. Cell Biol Toxicol 18:341–348 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Kohen, R. Skin antioxidants: their role in aging and in oxidative stress—new approaches for their evaluation. Biomed Pharmacother 53:181–192 (1999).

    Article  CAS  PubMed  Google Scholar 

  16. Gupta, M. A. & Gilchrest, B. A. Psychosocial aspects of aging skin. Dermatol Clin 23:643–648 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Lavker, R. M., Zheng, P. S. & Dong, G. Aged skin: a study by light, transmission electron, and scanning electron microscopy. J Invest Dermatol 88:44s–51s (1987).

    Article  CAS  PubMed  Google Scholar 

  18. Varani, J. et al. Inhibition of type I procollagen synthesis by damaged collagen in photoaged skin and by collagenase-degraded collagen in vitro. Am J Pathol 158:931–942 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. West, M. D. The cellular and molecular biology of skin aging. Arch Dermatol 130:87–95 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Fisher, G. J. et al. Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. J Clin Invest 101: 1432–1440 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kim, J. N., Kim, H. J., Jeong, S. H., Kye, Y. C. & Son, S. W. Cigarette smoke-induced early growth response-1 regulates the expression of the cysteine-rich 61 in human skin dermal fibroblasts. Exp Dermatol 20:992–997 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. Grzeszkiewicz, T. M., Lindner, V., Chen, N., Lam, S. C. & Lau, L. F. The angiogenic factor cysteine-rich 61 (CYR61, CCN1) supports vascular smooth muscle cell adhesion and stimulates chemotaxis through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans. Endocrinology 143:1441–1450 (2002).

    CAS  PubMed  Google Scholar 

  23. Edwards, D. R. et al. Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J 6:1899–1904 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Han, J. S., Macarak, E., Rosenbloom, J., Chung, K. C. & Chaqour, B. Regulation of Cyr61/CCN1 gene expression through RhoA GTPase and p38MAPK signaling pathways. Eur J Biochem 270:3408–3421 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. Laiho, M., Saksela, O., Andreasen, P. A. & Keski-Oja, J. Enhanced production and extracellular deposition of the endothelial-type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-beta. J Cell Biol 103:2403–2410 (1986).

    Article  CAS  PubMed  Google Scholar 

  26. Massague, J. The transforming growth factor-beta family. Annu Rev Cell Biol 6:597–641 (1990).

    Article  CAS  PubMed  Google Scholar 

  27. Yuan, W. & Varga, J. Transforming growth factor-beta repression of matrix metalloproteinase-1 in dermal fibroblasts involves Smad3. J Biol Chem 276:38502–38510 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Gashler, A. & Sukhatme, V. P. Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Nucleic Acid Res Mol Biol 50:191–224 (1995).

    Article  CAS  PubMed  Google Scholar 

  29. Harada, T., Morooka, T., Ogawa, S. & Nishida, E. ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1. Nat Cell Biol 3:453–459 (2001).

  30. Khachigian, L. M., Lindner, V., Williams, A. J. & Collins, T. Egr-1-induced endothelial gene expression: a common theme in vascular injury. Science 271:1427–1431 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Pagel, J. I. & Deindl, E. Early growth response 1-a transcription factor in the crossfire of signal transduction cascades. Indian J Biochem Biophys 48:226–235 (2011).

    CAS  PubMed  Google Scholar 

  32. Lee, H. et al. Chloroform upregulates early growth response-1-dependent thymic stromal lymphopoietin expression via the JNK and ERK pathways in human keratinocytes. Int J Dermatol 54:e521–526 (2015).

    Article  CAS  PubMed  Google Scholar 

  33. Jeong, S. H. et al. Up-regulation of TNF-alpha secretion by cigarette smoke is mediated by Egr-1 in HaCaT human keratinocytes. Exp Dermatol 19:e206–212 (2010).

    Article  PubMed  Google Scholar 

  34. Kim, J. N. et al. Cigarette smoke-induced Egr-1 represses T beta R-II expression in human skin dermal fibroblasts. Toxicology 275:29–35 (2010).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, Seoul, 02841, Republic of Korea

    Hana Lee, Jae Beom Park, Woo-In Ryu, Ji Hyun Kim, Jung Jin Shin & Sang Wook Son

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  1. Hana Lee
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  2. Jae Beom Park
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  3. Woo-In Ryu
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  4. Ji Hyun Kim
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  5. Jung Jin Shin
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  6. Sang Wook Son
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Correspondence to Sang Wook Son.

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These authors contributed equally to this work.

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Lee, H., Park, J.B., Ryu, WI. et al. Chloroform induces cystein-rich 61, a mediator of collagen homeostasis via early growth response-1 dependent pathway in human skin dermal fibroblasts. Mol. Cell. Toxicol. 12, 337–343 (2016). https://doi.org/10.1007/s13273-016-0038-6

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  • DOI: https://doi.org/10.1007/s13273-016-0038-6

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