Ann Dermatol.  2015 Oct;27(5):507-516. 10.5021/ad.2015.27.5.507.

Oxidative Damage and Nuclear Factor Erythroid 2-Related Factor 2 Protein Expression in Normal Skin and Keloid Tissue

Affiliations
  • 1Molecular Cancer Research, Soonchunhyang University College of Medicine, Cheonan, Korea.
  • 2Department of Dermatology, Soonchunhyang University Seoul Hospital, Seoul, Korea. mkcho2001@hanmail.net
  • 3Department of Plastic and Reconstruction Surgery, Soonchunhyang University Seoul Hospital, Seoul, Korea.
  • 4Department of Dermatology, Asan Medical Center, Seoul, Korea.

Abstract

BACKGROUND
Reactive oxygen species (ROS) play an important role in the induction of apoptosis under pathological conditions. Recently, a significant increase in ROS production and disrupted apoptosis mechanisms in keloids have been reported. Nuclear factor erythroid 2-related factor 2 (Nrf2) represents one of the most important cellular defense mechanisms against oxidative stress and is implicated in the regulation of apoptosis. Recently, it has been reported that Nrf2 upregulates Bcl-2, an anti-apoptotic protein.
OBJECTIVE
To compare Nrf2 protein expression in normal skin tissues to keloid tissues.
METHODS
ROS generation in keloid tissues was evaluated with OxyBlot analysis. Western blotting and/or immunohistochemical staining approaches were used to study expression of Nrf2 or Bcl-2 in keloid and normal skin tissues. Cellular fractionation was performed to examine subcellular distribution of Nrf2. Transfection of fibroblasts with Nrf2-specific small interfering RNA (siRNA) was conducted to understand the relationship between Nrf2 expression and apoptosis induction.
RESULTS
Protein oxidation, a marker of oxidative stress, is increased in keloid tissues. Western blot analysis clearly showed that Nrf2 and Bcl-2 are downregulated in keloid tissues. Immunohistochemical staining of Nrf2 confirmed the results of the western blot analysis. Transfection of fibroblasts with the Nrf2-specific siRNA results in increased apoptosis and decreased cell viability.
CONCLUSION
Collectively, our data indicate that Nrf2 expression is downregulated in keloid tissues, and that Nrf2 is involved in the development of apoptosis in Nrf2 siRNA-transfected fibroblasts. We propose that a defective antioxidant system and apoptotic dysregulation may participate in keloid pathogenesis.

Keyword

Apoptosis; BCL2; Keloid; NF-E2-related factor 2; Reactive oxygen species

MeSH Terms

Apoptosis
Blotting, Western
Cell Survival
Defense Mechanisms
Fibroblasts
Keloid*
NF-E2-Related Factor 2
Oxidative Stress
Reactive Oxygen Species
RNA, Small Interfering
Skin*
Transfection
NF-E2-Related Factor 2
RNA, Small Interfering
Reactive Oxygen Species
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