Targeting Angiogenesis by Blocking the ATM–SerRS–VEGFA Pathway for UV-Induced Skin Photodamage and Melanoma Growth
Abstract
:1. Introduction
2. Results
2.1. The ATM–SerRS–VEGFA Pathway Played an Essential Role in UV-Induced VEGFA Expression in HaCaT Cells
2.2. tRA Enhanced the Transcription of SerRS to Suppress VEGFA Expression in HaCaT Cells
2.3. ATM Inhibitor Enhanced the Effect of tRA on the Protection of Mouse Skin from UV-Induced VEGFA Expression
2.4. The ATM Inhibitor Improved the Efficiency of tRA Against Pathological Skin Angiogenesis Caused by UV Irradiation in Mice
2.5. ATM Inhibitor Improved the Effects of tRA on Alleviating UVB-Induced Thickening and the Inflammatory Response of the Epidermis
2.6. tRA and ATMi Could Greatly Inhibit UV-Induced VEGFA in Melanoma Cells
2.7. The ATM Inhibitor Greatly Improved the Effect of tRA in Inhibiting the Growth of a Melanoma Xenograft in Mice
3. Discussion
4. Materials and Methods
4.1. Regents and Antibodies
4.2. Cell Culture and UV Exposure
4.3. Animals and UVB Exposure
4.4. RNA Extraction and RT-PCR
4.5. Co-Immunoprecipitation Assay and Western Blotting Analysis
4.6. Measurement of VEGFA Secretion
4.7. H&E, Immunohistochemistry, and Immunofluorescent Staining
4.8. Dual-Luciferase Reporter Assay
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Score | Visual Manifestation |
---|---|
0 | Normal skin with a pink, smooth, and plump appearance |
0.5 | Mild erythema appearing at the exposed site |
1 | Moderate erythema, mild edema, and few scales |
1.5 | Obvious erythema and scales, with severe edema and mild roughness |
2 | Lots of scales, with hypertrophy and wrinkles |
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Song, Y.; Lu, H.; Wang, Q.; Xiang, R. Targeting Angiogenesis by Blocking the ATM–SerRS–VEGFA Pathway for UV-Induced Skin Photodamage and Melanoma Growth. Cancers 2019, 11, 1847. https://doi.org/10.3390/cancers11121847
Song Y, Lu H, Wang Q, Xiang R. Targeting Angiogenesis by Blocking the ATM–SerRS–VEGFA Pathway for UV-Induced Skin Photodamage and Melanoma Growth. Cancers. 2019; 11(12):1847. https://doi.org/10.3390/cancers11121847
Chicago/Turabian StyleSong, Yadong, Hongyan Lu, Qiong Wang, and Rong Xiang. 2019. "Targeting Angiogenesis by Blocking the ATM–SerRS–VEGFA Pathway for UV-Induced Skin Photodamage and Melanoma Growth" Cancers 11, no. 12: 1847. https://doi.org/10.3390/cancers11121847