Beneficial Regulation of Elastase Activity and Expression of Tissue Inhibitors of Matrixmetalloproteinases, Fibrillin, Transforming Growth Factor-, and Heat Shock Proteins by P. leucotomos in Nonirradiated or Ultraviolet-Radiated Epidermal Keratinocytes
There is loss of the structural integrity of the extracellular matrix (ECM) with intrinsic aging as well as photoaging, largely due to reactive oxygen species (ROS). The structural ECM proteins include the microfibrils that are composed of fibrillin. The structural ECM proteins are primarily degraded by the matrixmetalloproteinases (MMPs) and elastase enzymes. The MMPs are inhibited by the tissue inhibitors of MMPs (TIMPs). A primary regulator of the ECM proteins is transforming growth factor- (TGF- ), and the chaperone proteins important for its formation are the heat shock proteins (HSP). P. leucotomos extract beneficially regulates of MMPs, TIMPs, and TGF- in nonirradiated or ultraviolet (UV) radiated fibroblasts and melanoma cells. The hypothesis of this research was that the antioxidant activity or chemistry of P. leucotomos extract would also directly inhibit elastase activity, stimulate the cellular expression of TIMPs, fibrillins, and TGF- , and regulate HSPs in nonirradiated and UVA or UVB radiated epidermal keratinocytes. P. leucotomos directly inhibited elastase activity, stimulated the cellular expression of TIMPs, fibrillins, and TGF- , and differentially regulated HSPs in nonirradiated and UVA or UVB radiated epidermal keratinocytes. We infer that the P. leucotomos extract strengthens the ECM and is effective in the prevention or treatment of intrinsic and photoaging of skin. 1. Introduction Cellular oxidative stress from increased reactive oxygen species (ROS) occurs with intrinsic aging, and more so from the exposure of skin to ultraviolet (UV) radiation. The UV radiation includes the long-wavelength UV-A light (320–400?nm), which increases cellular ROS and ROS mediated cellular/extracellular matrix (ECM) damage, and the short-wavelength UV-B light (290–320?nm), which directly damages DNA as well as cells/ECM through ROS. The ROS facilitate the degradation/remodeling of the ECM that leads to skin aging or cancer. The ECM proteins include the microfibrillar network that is composed of the fibrillin, synthesized by the epidermal keratinocytes and the dermal fibroblasts. The degradation of the ECM proteins is primarily by the matrixmetalloproteinases (MMPs) and elastase, which are inhibited by the cellular inhibitors of MMPs, tissue inhibitors of MMPs (TIMPs). The primary regulator of the ECM is transforming growth factor- (TGF- ). Antioxidants remove ROS, and thereby have the potential to inhibit ROS mediated skin aging or cancer. Polypodium leucotomos is a topical fern plant of the order polypodiaceae. P. leucotomos is rich in polyphenols
References
[1]
L. Gombau, F. García, A. Lahoz et al., “Polypodium leucotomos extract: antioxidant activity and disposition,” Toxicology in Vitro, vol. 20, no. 4, pp. 464–471, 2006.
[2]
N. Philips, J. Smith, T. Keller, and S. Gonzalez, “Predominant effects of Polypodium leucotomos on membrane integrity, lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1 in ultraviolet radiation exposed fibroblasts, and keratinocytes,” Journal of Dermatological Science, vol. 32, no. 1, pp. 1–9, 2003.
[3]
N. Philips, J. Conte, Y.-J. Chen et al., “Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-β by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells,” Archives of Dermatological Research, vol. 301, no. 7, pp. 487–495, 2009.
[4]
R. E. B. Watson, C. E. M. Griffiths, N. M. Craven, C. A. Shuttleworth, and C. M. Kielty, “Fibrillin-rich microfibrils are reduced in photoaged skin. Distribution at the dermal-epidermal junction,” Journal of Investigative Dermatology, vol. 112, no. 5, pp. 782–787, 1999.
[5]
R. E. B. Watson, N. M. Craven, S. Kang, C. J. P. Jones, C. M. Kielty, and C. E. M. Griffiths, “A short-term screening protocol, using fibrillin-1 as a reporter molecule, for photoaging repair agents,” Journal of Investigative Dermatology, vol. 116, no. 5, pp. 672–678, 2001.
[6]
R. E. Watson, S. Ogden, L. F. Cotterell et al., “Effects of a cosmetic “anti-ageing” product improves photoaged skin [corrected],” The British Journal of Dermatology, vol. 161, no. 2, pp. 419–426, 2009.
[7]
N. Philips, T. Keller, and S. Gonzalez, “TGF β-like regulation of matrix metalloproteinases by anti-transforming growth factor-β, and anti-transforming growth factor-β1 antibodies in dermal fibroblasts: implications for wound healing,” Wound Repair and Regeneration, vol. 12, no. 1, pp. 53–59, 2004.
[8]
N. Philips and N. Onwubalili, “Anti transforming growth factor-beta (TGF-β) increases the expressions of matrix metalloproteinase-1 (MMP-1) and growth factors in a renal adenocarcinoma cell line,” BIOS, vol. 73, pp. 86–90, 2002.
[9]
G. Zeng, H. M. McCue, L. Mastrangelo, and A. J. T. Millis, “Endogenous TGF-β activity is modified during cellular aging: Effects on metalloproteinase and TIMP-1 expression,” Experimental Cell Research, vol. 228, no. 2, pp. 271–276, 1996.
[10]
N. Philips, R. Arena, and S. Yarlagadda, “Inhibition of ultraviolet radiation mediated extracellular matrix remodeling in fibroblasts by transforming growth factor-b,” BIOS, vol. 80, article 1, 2009.
[11]
N. Philips, “An anti TGF-β antibody increased the expression of transforming growth factor-β, matrix metalloproteinase-1, and elastin, and its effects were antagonized by ultraviolet radiation in epidermal keratinocytes,” Journal of Dermatological Science, vol. 33, no. 3, pp. 177–179, 2003.
[12]
C. Jonak, M. Mildner, G. Klosner et al., “The hsp27kD heat shock protein and p38-MAPK signaling are required for regular epidermal differentiation,” Journal of Dermatological Science, vol. 61, no. 1, pp. 32–37, 2011.
[13]
M. Matsuda, T. Hoshino, Y. Yamashita et al., “Prevention of UVB radiation-induced epidermal damage by expression of heat shock protein 70,” Journal of Biological Chemistry, vol. 285, no. 8, pp. 5848–5858, 2010.
[14]
A. Gutsmann-Conrad, A. R. Heydari, S. You, and A. Richardson, “The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects,” Experimental Cell Research, vol. 241, no. 2, pp. 404–413, 1998.
[15]
F. Rijken, R. C. M. Kiekens, and P. L. B. Bruijnzeel, “Skin-infiltrating neutrophils following exposure to solar-simulated radiation could play an important role in photoageing of human skin,” British Journal of Dermatology, vol. 152, no. 2, pp. 321–328, 2005.
[16]
N. Tsuji, S. Moriwaki, Y. Suzuki, Y. Takema, and G. Imokawa, “The role of elastases secreted by fibroblasts in wrinkle formation: implication through selective inhibition of elastase activity,” Photochemistry and Photobiology, vol. 71, pp. 283–290, 2001.
[17]
J. Labat-Robert, A. Fourtanier, B. Boyer-Lafargue, and L. Robert, “Age dependent increase of elastase type protease activity in mouse skin effect of UV-irradiation,” Journal of Photochemistry and Photobiology B, vol. 57, no. 2-3, pp. 113–118, 2000.
[18]
N. Philips, T. Keller, C. Hendrix et al., “Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts,” Archives of Dermatological Research, vol. 299, no. 8, pp. 373–379, 2007.
[19]
H. Zhang, W. Hu, and F. Ramirez, “Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils,” Journal of Cell Biology, vol. 129, no. 4, pp. 1165–1176, 1995.
[20]
F. Ramirez and L. Pereira, “The fibrillins,” International Journal of Biochemistry and Cell Biology, vol. 31, no. 2, pp. 255–259, 1999.
[21]
H. H. Kim, S. Cho, S. Lee et al., “Photoprotective and anti-skin-aging effects of eicosapentaenoic acid in human skin in vivo,” Journal of Lipid Research, vol. 47, no. 5, pp. 921–930, 2006.
[22]
N. Philips, L. Dulaj, and T. Upadhya, “Growth inhibitory mechanism of ascorbate and counteraction of its matrix metalloproteinases-1 and transforming growth factor-beta stimulation by gene silencing or P. leucotomos,” AntiCancer Research, vol. 29, pp. 3233–3238, 2008.