Oxidative Damage and Nuclear Factor Erythroid 2-Related Factor 2 Protein Expression in Normal Skin and Keloid Tissue.
- Author:
Yoon Jin LEE
1
;
Sun Bum KWON
;
Chul Han KIM
;
Hyun Deuk CHO
;
Hae Seon NAM
;
Sang Han LEE
;
Mi Woo LEE
;
Doo Hyun NAM
;
Chang Yong CHOI
;
Moon Kyun CHO
Author Information
- Publication Type:Original Article
- Keywords: Apoptosis; BCL2; Keloid; NF-E2-related factor 2; Reactive oxygen species
- MeSH: Apoptosis; Blotting, Western; Cell Survival; Defense Mechanisms; Fibroblasts; Keloid*; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species; RNA, Small Interfering; Skin*; Transfection
- From:Annals of Dermatology 2015;27(5):507-516
- CountryRepublic of Korea
- Language:English
- 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.
