The impact of non-toxic blue light (453 nm) on cellular antioxidative capacity, TGF-β1 signaling, and myofibrogenesis of human skin fibroblasts

TY - JOUR

T1 - The impact of non-toxic blue light (453 nm) on cellular antioxidative capacity, TGF-β1 signaling, and myofibrogenesis of human skin fibroblasts

AU - Krassovka, Julia M

AU - Suschek, Christoph V

AU - Prost, Max

AU - Grotheer, Vera

AU - Schiefer, Jennifer L

AU - Demir, Erhan

AU - Fuchs, Paul C

AU - Windolf, Joachim

AU - Stürmer, Ewa K

AU - Opländer, Christian

N1 - Copyright © 2020 Elsevier B.V. All rights reserved.

PY - 2020/8

Y1 - 2020/8

N2 - Studies have demonstrated that blue light induces biological effects, such as cell death, and inhibition of proliferation and differentiation. Since blue light at longer wavelength (>440 nm) exerts less injurious effects on cells than at shorter wavelengths, (400-440 nm), we have investigated the impact of non-toxic (LED) blue light at 453 nm wavelength on human skin fibroblasts (hsFBs). We found that besides its decreasing effects on the proliferation rate, repeated blue light irradiations (80 J/cm2) also significantly reduced TGF-β1-induced myofibrogenesis as shown by diminished α-SMA and EDA-FN expression accompanied by reduced protein expression and phosphorylation of ERK 1/2, SMAD 2/3, and p38-key players of TGF-β1-induced myofibrogenesis. In parallel, catalase protein expression, intracellular FAD concentrations as well as NADP+/NADPH ratio were reduced, whereas intracellular reactive oxygen species (ROS) were increased. We postulate that as a molecular mechanism downregulation of catalase and photoreduction of FAD induce intracellular oxidative stress which, in turn, affects the signaling factors of myofibrogenesis leading to a lower rate of α-SMA and EDA-FN expression and, therefore, myofibroblast formation. In conclusion, blue light even at longer wavelengths shows antifibrotic activity and may represent a suitable and safe approach in the treatment of fibrotic skin diseases including hypertrophic scarring and scleroderma.

AB - Studies have demonstrated that blue light induces biological effects, such as cell death, and inhibition of proliferation and differentiation. Since blue light at longer wavelength (>440 nm) exerts less injurious effects on cells than at shorter wavelengths, (400-440 nm), we have investigated the impact of non-toxic (LED) blue light at 453 nm wavelength on human skin fibroblasts (hsFBs). We found that besides its decreasing effects on the proliferation rate, repeated blue light irradiations (80 J/cm2) also significantly reduced TGF-β1-induced myofibrogenesis as shown by diminished α-SMA and EDA-FN expression accompanied by reduced protein expression and phosphorylation of ERK 1/2, SMAD 2/3, and p38-key players of TGF-β1-induced myofibrogenesis. In parallel, catalase protein expression, intracellular FAD concentrations as well as NADP+/NADPH ratio were reduced, whereas intracellular reactive oxygen species (ROS) were increased. We postulate that as a molecular mechanism downregulation of catalase and photoreduction of FAD induce intracellular oxidative stress which, in turn, affects the signaling factors of myofibrogenesis leading to a lower rate of α-SMA and EDA-FN expression and, therefore, myofibroblast formation. In conclusion, blue light even at longer wavelengths shows antifibrotic activity and may represent a suitable and safe approach in the treatment of fibrotic skin diseases including hypertrophic scarring and scleroderma.

KW - Antioxidants/metabolism

KW - Cell Proliferation/radiation effects

KW - Humans

KW - Light

KW - Myofibroblasts/cytology

KW - Oxidative Stress

KW - Signal Transduction/radiation effects

KW - Transforming Growth Factor beta1/metabolism

U2 - 10.1016/j.jphotobiol.2020.111952

DO - 10.1016/j.jphotobiol.2020.111952

M3 - SCORING: Journal article

C2 - 32659647

VL - 209

JO - J PHOTOCH PHOTOBIO B

JF - J PHOTOCH PHOTOBIO B

SN - 1011-1344

M1 - 111952

ER -