Role of Nrf2 in photoaging and epidermal keratinization

• Project/Area Number: 24591642
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tokyo Medical University (2014); University of Tsukuba (2012-2013)
• Principal Investigator: KAWACHI Yasuhiro 東京医科大学, 医学部, 教授 (00272196)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 光老化 / 酸化ストレス / Nrf2 / 紫外線 / 皮膚

Outline of Final Research Achievements

Ultraviolet (UV) radiation is one of the most important environmental factors involved in the pathogenesis of premature skin aging, termed photoaging. The harmful effects of UV in photoaging are associated with the generation of reactive oxygen species, and cellular antioxidants act to prevent the occurrence and reduce the severity of UV-induced photoaging. Nrf2 and Keap1 are central regulators of the cellular antioxidant response. Here, we investigated the role of the Nrf2-Keap1 pathway in photoaging using nrf2 gene-deficient (nrf2-/-) mice. Our results indicated that UVB-irradiated nrf2-/- mice showed accelerated photoaging, such as coarse wrinkle formation, loss of skin flexibility, epidermal thickening, and deposition of extracellular matrix in the upper dermis. In addition, nrf2-/- mice also showed a significant decrease in cutaneous glutathione level. These findings indicate that Nrf2 plays the important role in the protection against UVB-induced photoaging.

Research Products

• [Journal Article] Angiosarcoma of the scalp in a patient with systemic sclerosis. (2015)
  • Author(s): Kubota N, Fujisawa Y, Nakamura Y, Tanaka R, Saito A, Maruyama H, Ishii Y, Furutra J, Kawachi Y, Fujimoto M.
  • Journal Title: J Dermatol Volume: 42 Issue: 1 Pages: 102-104
  • DOI: 10.1111/1346-8138.12705
  • Peer Reviewed
• [Journal Article] Case of pigmented epithelioid melanocytoma with lymph node metastases. (2014)
  • Author(s): Fujisawa Y, Maruyama H, Furuta J, Ishii Y, Kawachi Y, Fujimoto M.
  • Journal Title: J Dermatol. Volume: 41 Issue: 5 Pages: 452-453
  • DOI: 10.1111/1346-8138.12482
  • Peer Reviewed
• [Journal Article] Dermatofibrosarcoma protuberans mimicking cutaneous sarcoidosis in a patient with lung sarcoidosis. (2014)
  • Author(s): Fujisawa Y, Furuta J, Kawachi Y.
  • Journal Title: Eur J Dermatol Volume: 24 Issue: 2 Pages: 276-277
  • DOI: 10.1684/ejd.2014.2310
  • Peer Reviewed
• [Journal Article] B-Myb enhances proliferation and suppresses differentiation of keratinocytes in three-dimensional cell culture. (2014)
  • Author(s): Maruyama H, Ishitsuka Y, Fujisawa Y, Furuta J, Sekido M, Kawachi Y.
  • Journal Title: Arch Dermatol Res. Volume: 306 Issue: 4 Pages: 375-384
  • DOI: 10.1007/s00403-014-1450-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Peroxiredoxin I plays a protective role against UVA irradiation through reduction of oxidative stress. (2014)
  • Author(s): Ito T, Kimura S, Seto K, Warabi E, Kawachi Y, Shoda J, Tabuchi K, Yamagata K, Hasegawa S, Bukawa H, Ishii T, Yanagawa T.
  • Journal Title: J Dermatol Sci. Volume: 74 Issue: 1 Pages: 9-17
  • DOI: 10.1016/j.jdermsci.2013.12.002
  • Peer Reviewed
• [Journal Article] Pituitary Tumor Transforming Gene 1 Induces Tumor Necrosis Factor-αProduction from Keratinocytes : Implication for Involvement in the Pathophysiology of Psoriasis (2013)
  • Author(s): Ishitsuka Y, Kawachi Y, Maruyama H, Taguchi S, Fujisawa Y, Furuta J, Nakamura Y, Ishii Y, Otsuka F.
  • Journal Title: J Invest Dermatol Volume: 133(11) Issue: 11 Pages: 2566-2575
  • DOI: 10.1038/jid.2013.189
  • Peer Reviewed
• [Journal Article] GATA-3 regulates differentiation-specific loricrin gene expression in keratinocytes. (2012)
  • Author(s): 9. Kawachi Y, Ishitsuka Y, Maruyama H, Fujisawa Y, Furuta J, Nakamura Y, Otsuka F
  • Journal Title: Exp Dermatol Volume: 21 Pages: 859-864
  • Peer Reviewed
• [Journal Article] Pituitary tumor-transforming gene 1 enhances proliferation and suppresses early differentiation of keratinocytes. (2012)
  • Author(s): Ishitsuka Y, Kawachi Y, Taguchi S, Maruyama H, Fujisawa Y, Furuta J, Nakamura Y, Otsuka F
  • Journal Title: J Invest Dermatol Volume: 132 Pages: 1775-1784
  • NAID: 120007137074
  • Peer Reviewed