MSC-Exosomes Hypoxia (EH-MSCs) in modulating Apaf-1 and Survivin in UVB-induced skin aging
Abstract
Skin aging is marked by decreased elasticity and increased wrinkle formation, often associated with altered expression of key genes such as APAF-1 and Survivin. Exposure to UVB radiation, particularly in tropical regions, accelerates collagen degradation, thereby heightening the risk of premature aging. Mesenchymal stem cell-derived hypoxic exosomes (MSCs-Exosome Hipoksia) have shown potential in suppressing APAF-1 expression and enhancing Survivin levels, although their effects on UVB-induced skin damage have not been fully explored. This study investigated the impact of MSCs-Exosome Hipoksia on APAF-1 and Survivin gene expression in UVB-exposed rat skin. Rats with reduced collagen levels due to UVB exposure were randomly assigned into four groups: normal control (KN; UVB + 0.9% sodium chloride 300 µL), positive control (KP; UVB + hyaluronic acid 200 µL), treatment group 1 (T1; UVB + MSCs-Exosome Hipoksia 200 µL), and treatment group 2 (T2; UVB + MSCs-Exosome Hipoksia 300 µL). The T2 group demonstrated the lowest APAF-1 expression (1.03 ± 0.33 pg/mL) and the highest Survivin expression (4.35 ± 0.73 pg/mL). Both treatment groups (T1 and T2) showed statistically significant reductions in APAF-1 and increases in Survivin expression compared to control groups (p < 0.05). These findings indicate that MSCs-Exosome Hipoksia, particularly at a dose of 300 µL, may effectively modulate molecular markers associated with skin aging and hold therapeutic potential in mitigating UVB-induced dermal damage.
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References
- 1. Bosch R, Philips N, Suárez-Pérez JA, et al. Mechanisms of photoaging and cutaneous photocarcinogenesis, and photoprotective strategies with phytochemicals. Antioxidants. 2015;4(2):248-268. doi:10.3390/antiox4020248
- 2. Lin H, Pan Y, Cai S. Direct Lineage Reprogramming for Induced Keratinocyte Stem Cells: A Potential Approach for Skin Repair. Stem Cells Transl Med. 2023;12(5):245-257. doi:10.1093/stcltm/szad019
- 3. Zhu S, Sun C, Zhang L, Du X, Tan X, Peng S. Incidence Trends and Survival Prediction of Malignant Skin Cancer: A SEER-Based Study. Int J Gen Med. 2022;15:2945-2956. doi:10.2147/IJGM.S340620
- 4. Fu M, Xie D, Sun Y, et al. Exosomes derived from MSC pre-treated with oridonin alleviates myocardial IR injury by suppressing apoptosis via regulating autophagy activation. J Cell Mol Med. 2021;25(12):5486-5496. doi:10.1111/jcmm.16558
- 5. Albadari N, Li W. Survivin Small Molecules Inhibitors: Recent Advances and Challenges. Molecules. 2023;28(3). doi:10.3390/molecules28031376
- 6. Labarrade F, Bergeron L, Serre C, et al. Modulating the Expression of Survivin and Other Basal Epidermal Proteins Protects Human Skin from UVB Damage and Oxidative Stress. Vol 14.; 2015.
- 7. Mokuda S, Miyazaki T, Ito Y, et al. The proto-oncogene survivin splice variant 2B is induced by PDGF and leads to cell proliferation in rheumatoid arthritis fibroblast-like synoviocytes. Sci Rep. 2015;5. doi:10.1038/srep09795
- 8. Mahmoudi MB, Farashahi Yazd E, Gharibdoost F, et al. Overexpression of apoptosis-related protein, survivin, in fibroblasts from patients with systemic sclerosis. Ir J Med Sci. 2019;188(4):1443-1449. doi:10.1007/s11845-019-01978-w
- 9. Shojaei-Ghahrizjani F, Rahmati S, Mirzaei SA, Banitalebi-Dehkordi M. Does survivin overexpression enhance the efficiency of fibroblast cell-based wound therapy? Mol Biol Rep. 2020;47(8):5851-5864. doi:10.1007/s11033-020-05656-4
- 10. Li XZ, Chiang CF, Lin YH, et al. Safety and efficacy of hyaluronic acid injectable filler in the treatment of nasolabial fold wrinkle: a randomized, double-blind, self-controlled clinical trial. Journal of Dermatological Treatment. 2023;34(1). doi:10.1080/09546634.2023.2190829
- 11. Jang M, Baek S, Kang G, Yang H, Kim S, Jung H. Dissolving microneedle with high molecular weight hyaluronic acid to improve skin wrinkles, dermal density and elasticity. Int J Cosmet Sci. 2020;42(3):302-309. doi:10.1111/ics.12617
- 12. Cao J, Wang B, Tang T, et al. Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury. Stem Cell Res Ther. 2020;11(1). doi:10.1186/s13287-020-01719-2
- 13. Lee JY, Chung J, Byun Y, Kim KH, An SH, Kwon K. Mesenchymal stem cell-derived small extracellular vesicles protect cardiomyocytes from doxorubicin-induced cardiomyopathy by upregulating survivin expression via the mir-199a-3p-akt-sp1/p53 signaling pathway. Int J Mol Sci. 2021;22(13). doi:10.3390/ijms22137102
- 14. De Mendonça L, Felix NS, Blanco NG, et al. Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension. Stem Cell Res Ther. 2017;8(1). doi:10.1186/s13287-017-0669-0
- 15. Shah K, Minkis K, Swary JH, Alam M. Photoaging. In: Cosmetic Dermatology: Products and Procedures. ; 2022. doi:10.1002/9781119676881.ch2
- 16. Singh J, Chopra D, Dwivedi A, Ray RS. Photoaging. In: Photocarcinogenesis and Photoprotection. ; 2018. doi:10.1007/978-981-10-5493-8_7
- 17. Glady A, Tanaka M, Moniaga CS, Yasui M, Hara-Chikuma M. Involvement of NADPH oxidase 1 in UVB-induced cell signaling and cytotoxicity in human keratinocytes. Biochem Biophys Rep. Published online 2018. doi:10.1016/j.bbrep.2018.03.004
- 18. Ansary TM, Hossain MR, Kamiya K, Komine M, Ohtsuki M. Inflammatory molecules associated with ultraviolet radiation?mediated skin aging. Int J Mol Sci. 2021;22(8). doi:10.3390/ijms22083974
- 19. Wu Y, Huang S, Enhe J, et al. Bone marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice. Int Wound J. 2014;11(6):701-710. doi:10.1111/iwj.12034
- 20. Martin-Piedra MA, Alfonso-Rodriguez CA, Zapater A, et al. Effective use of mesenchymal stem cells in human skin substitutes generated by tissue engineering. Eur Cell Mater. 2019;37:233-249. doi:10.22203/ECM.V037A14
- 21. Wang W, Li P, Li W, et al. Osteopontin activates mesenchymal stem cells to repair skin wound. PLoS One. 2017;12(9). doi:10.1371/journal.pone.0185346
- 22. Lai P, Weng J, Guo L, Chen X, Du X. Novel insights into MSC-EVs therapy for immune diseases. Biomark Res. 2019;7(1). doi:10.1186/s40364-019-0156-0
- 23. Ubels JL, Glupker CD, Schotanus MP, Haarsma LD. Involvement of the extrinsic and intrinsic pathways in ultraviolet B-induced apoptosis of corneal epithelial cells. Exp Eye Res. 2016;145:26-35. doi:10.1016/j.exer.2015.11.003
- 24. Chen J, Chen J, Cheng Y, et al. Mesenchymal stem cell-derived exosomes protect beta cells against hypoxia-induced apoptosis via miR-21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation. Stem Cell Res Ther. 2020;11(1). doi:10.1186/s13287-020-01610-0
- 25. Zhu LP, Tian T, Wang JY, et al. Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction. Theranostics. 2018;8(22):6163-6177. doi:10.7150/thno.28021
- 26. Luan Z, Liu J, Li M, Wang Y, Wang Y. Exosomes derived from umbilical cord-mesenchymal stem cells inhibit the NF-?B/MAPK signaling pathway and reduce the inflammatory response to promote recovery from spinal cord injury. J Orthop Surg Res. 2024;19(1). doi:10.1186/s13018-024-04651-w
- 27. Zhang Y, Xu Y, Zhou K, Kao G, Xiao J. MicroRNA 126 and VEGF enhance the function of endothelial progenitor cells in acute myocardial infarction. Exp Ther Med. 2021;23(2). doi:10.3892/etm.2021.11065
- 28. Pan Q, Wang Y, Lan Q, et al. Exosomes derived from mesenchymal stem cells ameliorate hypoxia/reoxygenation-injured ECs via transferring MicroRNA-126. Stem Cells Int. 2019;2019. doi:10.1155/2019/2831756
- 29. Minoves M, Hazane-Puch F, Moriondo G, et al. Differential Impact of Intermittent vs. Sustained Hypoxia on HIF-1, VEGF and Proliferation of HepG2 Cells. Int J Mol Sci. 2023;24(8). doi:10.3390/ijms24086875
- 30. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18(9). doi:10.3390/ijms18091852
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