PARP‐1 involves in UVB‐induced inflammatory response in keratinocytes and skin injury via regulation of ROS‐dependent EGFR transactivation and p38 signaling
Open Access
- 11 February 2021
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 35 (3), e21393
- https://doi.org/10.1096/fj.202002285rr
Abstract
UV irradiation can injure the epidermis, resulting in sunburn, inflammation, and cutaneous tissue disorders. Previous studies demonstrate that EGFR in keratinocytes can be activated by UVB and contributes to inflammation. Poly (ADP‐ribose) polymerase‐1 (PARP‐1) is a nuclear enzyme and plays an essential role in DNA repair under moderate stress. In this study, we set out to understand how PARP‐1 regulates UVB irradiation‐induced skin injury and interplays with EGFR to mediate the inflammation response. We found that PARP‐1 deficiency exacerbated the UVB‐induced inflammation, water loss, and back skin damage in mice. In human primary keratinocytes, UVB can activate PARP‐1 and enhance DNA damage upon PARP‐1 gene silencing. Moreover, PARP‐1 silencing and PARP inhibitor olaparib can suppress UVB‐induced COX‐2 and MMP‐1 expression, but enhance TNF‐α and IL‐8 expression. In addition, EGFR silencing or EGFR inhibition by gefitinib can decrease UVB‐induced COX‐2, TNF‐α, and IL‐8 expression, suggesting EGFR activation via paracrine action can mediate UVB‐induced inflammation responses. Immunoblotting data revealed that PARP‐1 inhibition decreases UVB‐induced EGFR and p38 activation. Pharmacological inhibition of p38 also dramatically led to the attenuation of UVB‐induced inflammatory gene expression. Of note, genetic ablation of PARP‐1 or EGFR can attenuate UVB‐induced ROS production, and antioxidant NAC can attenuate UVB‐induced EGFR‐p38 signaling axis and PARP‐1 activation. These data suggest the regulatory loops among EGFR, PARP‐1, and ROS upon UVB stress. PARP‐1 not only serves DNA repair function but also orchestrates interactions to EGFR transactivation and ROS production, leading to p38 signaling for inflammatory gene expression in keratinocytes.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (MOST 107‐2911‐I‐002‐544)
- Ministry of Science and Technology, Taiwan (MOST 108‐2911‐I‐002‐513)
- Ministry of Science and Technology, Taiwan (NKM‐26/2019)
- Academia Sinica (AS‐TP‐106‐L11)
- College of Medicine, National Taiwan University (NSCCMOH‐94‐51)
- College of Medicine, National Taiwan University (NSCCMOH‐131‐21)
- National Taiwan University Hospital (109‐M4754)
This publication has 59 references indexed in Scilit:
- The Epidermal Growth Factor Receptor Increases Cytokine Production and Cutaneous Inflammation in Response to Ultraviolet IrradiationISRN Dermatology, 2013
- Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repairProceedings of the National Academy of Sciences of the United States of America, 2013
- Anti-Photoaging Effects of Soy Isoflavone Extract (Aglycone and Acetylglucoside Form) from Soybean CakeInternational Journal of Molecular Sciences, 2010
- Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytesBiochemical and Biophysical Research Communications, 2010
- Requirement for Metalloproteinase‐dependent ERK and AKT Activation in UVB‐induced G1‐S Cell Cycle Progression of Human KeratinocytesPhotochemistry and Photobiology, 2009
- The Inflammasome Mediates UVB-Induced Activation and Secretion of Interleukin-1β by KeratinocytesCurrent Biology, 2007
- Epidermal Growth Factor Receptor Is a Critical Mediator of Ultraviolet B Irradiation-Induced Signal Transduction in Immortalized Human Keratinocyte HaCaT CellsThe American Journal of Pathology, 2006
- Effect of Cyanidin-3-O-glucoside on UVB-Induced Response in Human KeratinocytesJournal of Agricultural and Food Chemistry, 2006
- RhoB Protects Human Keratinocytes from UVB-induced Apoptosis through Epidermal Growth Factor Receptor SignalingOnline Journal of Public Health Informatics, 2005
- Epidermal Growth Factor Receptor-dependent, NF-κB-independent Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Inhibits Ultraviolet Irradiation-induced Caspases-3, -8, and -9 in Human KeratinocytesOnline Journal of Public Health Informatics, 2003