Hypoxia-preconditioned MSC-derived exosomes suppress IL-1beta and caspase-1 expression in a UVB-induced skin damage model
Abstract
Ultraviolet B (UVB) irradiation induces skin damage characterized by collagen degradation and enhanced inflammatory responses. Hypoxia-preconditioned exosomes derived from mesenchymal stem cells (MSCs) have emerged as a potential therapeutic strategy due to their anti-inflammatory and regenerative properties. This study aimed to evaluate the effects of hypoxia-preconditioned MSC-derived exosomes on IL-1beta and caspase-1 gene expression in a UVB-induced skin damage model. An in vivo experimental study was conducted using 30 male Wistar rats divided into three groups: control, UVB-exposed, and UVB-exposed treated with hypoxia-preconditioned MSC-derived exosomes. UVB irradiation was administered for four weeks to induce collagen degradation, followed by weekly exosome injections in the treatment group. Gene expression levels of IL-1beta and caspase-1 in skin tissue were quantified using qRT-PCR. UVB exposure significantly increased IL-1beta and caspase-1 expression compared with the control group. Treatment with hypoxia-preconditioned MSC-derived exosomes significantly reduced the expression of both inflammatory markers compared with the untreated UVB group. These findings demonstrate that hypoxia-preconditioned MSC-derived exosomes attenuate inflammasome-associated inflammatory responses and may represent a promising therapeutic approach for mitigating UVB-induced skin damage.
There is no Figure or data content available for this article
References
- 1. Cai J, Wu J, Wang J, et al. Extracellular vesicles derived from different sources of mesenchymal stem cells: Therapeutic effects and translational potential. Cell Biosci. BioMed Central Ltd. 2020;10(1). doi:10.1186/s13578-020-00427-x
- 2. Robert AW, Marcon BH, Angulski ABB, et al. Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia. Int J Mol Sci. 2022;23(17). doi:10.3390/ijms231710066
- 3. Yang XX, Zhao MM, He YF, et al. Facial Skin Aging Stages in Chinese Females. Front Med (Lausanne). 2022;9. doi:10.3389/fmed.2022.870926
- 4. Watson REB, Gibbs NK, Griffiths CEM, Sherratt MJ. Damage to skin extracellular matrix induced by UV exposure. Antioxid Redox Signal. Mary Ann Liebert Inc. 2014;21(7):1063-1077. doi:10.1089/ars.2013.5653
- 5. Son DJ, Jung JC, Choi YM, Ryu HY, Lee S, Davis BA. Wheat extract oil (WEO) attenuates UVB-induced photoaging via collagen synthesis in human keratinocytes and hairless mice. Nutrients. 2020;12(2):1-13. doi:10.3390/nu12020300
- 6. Poon F, Kang S, Chien AL. Mechanisms and treatments of photoaging. Photodermatol Photoimmunol Photomed. Blackwell Publishing Ltd. 2015;31(2):65-74. doi:10.1111/phpp.12145
- 7. Putra A, Pertiwi D, Milla MN, et al. Hypoxia-preconditioned MSCs have superior effect in ameliorating renal function on acute renal failure animal model. Open Access Maced J Med Sci. 2019;7(3):305-310. doi:10.3889/oamjms.2019.049
- 8. Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 2011;22(4):189-195. doi:10.1016/j.cytogfr.2011.10.001
- 9. Almi, DU, Sarosa, H, Trisnadi S. The Effect of Sapodilla Leaf Extract (Manilkara Zapota L.P Royen) on IL-1 and TNF- α Expression in Male White Rats Wistar Strain Induced with UVB Light. International Journal Of Multidisciplinary Research And Analysis. 2024;07(02). doi:10.47191/ijmra/v7-i02-48
- 10. Chen L, Chen R, Wang H, Liang F. Mechanisms Linking Inflammation to Insulin Resistance. Int J Endocrinol. Hindawi Limited. 2015;2015. doi:10.1155/2015/508409
- 11. Shi Y, Yang X, Wang S, et al. Human umbilical cord mesenchymal stromal cell-derived exosomes protect against MCD-induced NASH in a mouse model. Stem Cell Res Ther. 2022;13(1). doi:10.1186/s13287-022-03201-7
- 12. Xiu C, Zheng H, Jiang M, et al. MSCs-Derived miR-150-5p-Expressing Exosomes Promote Skin Wound Healing by Activating PI3K/AKT Pathway through PTEN. Int J Stem Cells. 2022;15(4):359-371. doi:10.15283/ijsc21135
- 13. Kim SR, Zou X, Tang H, et al. Increased cellular senescence in the murine and human stenotic kidney: Effect of mesenchymal stem cells. J Cell Physiol. 2021;236(2):1332-1344. doi:10.1002/jcp.29940
- 14. Shen C, Tao C, Zhang A, et al. Exosomal microRNA⁃93⁃3p secreted by bone marrow mesenchymal stem cells downregulates apoptotic peptidase activating factor 1 to promote wound healing. Bioengineered. 2022;13(1):27-37. doi:10.1080/21655979.2021.1997077
- 15. Edye ME, Lopez-Castejon G, Allan SM, Brough D. Acidosis drives damage-associated molecular pattern (DAMP)-induced interleukin-1 secretion via a caspase-1-independent pathway. Journal of Biological Chemistry. 2013;288(42):30485-30494. doi:10.1074/jbc.M113.478941
- 16. Mori K, Uchida T, Yoshie T, et al. A mitochondrial ROS pathway controls matrix metalloproteinase 9 levels and invasive properties in RAS-activated cancer cells. FEBS Journal. 2019;286(3):459-478. doi:10.1111/febs.14671
- 17. Deng C, Dong K, Liu Y, et al. Hypoxic mesenchymal stem cell-derived exosomes promote the survival of skin flaps after ischaemia–reperfusion injury via mTOR/ULK1/FUNDC1 pathways. J Nanobiotechnology. 2023;21(1). doi:10.1186/s12951-023-02098-5
- 18. Yu Y, Li W, Xian T, Tu M, Wu H, Zhang J. Human Embryonic Stem-Cell-Derived Exosomes Repress NLRP3 Inflammasome to Alleviate Pyroptosis in Nucleus Pulposus Cells by Transmitting miR-302c. Int J Mol Sci. 2023;24(8). doi:10.3390/ijms24087664
- 19. Li J, Lin X, Wang J, et al. Dendritic Cell Repression by TNF-α-Primed Exosomes Accelerate T2DM Wound Healing Through miR-146a-5p/TXNIP/NLRP3 Axis. Int J Nanomedicine. 2025;20:9963-9980. doi:10.2147/IJN.S522994
- 20. Bonnici L, Suleiman S, Schembri-Wismayer P, Cassar A. Targeting Signalling Pathways in Chronic Wound Healing. Int J Mol Sci. Multidisciplinary Digital Publishing Institute (MDPI). 2024;25(1). doi:10.3390/ijms25010050
- 21. Lotfy A, AboQuella NM, Wang H. Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials. Stem Cell Res Ther. BioMed Central Ltd. 2023;14(1). doi:10.1186/s13287-023-03287-7
- 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. Scuteri A, Monfrini M. Mesenchymal stem cells as new therapeutic approach for diabetes and pancreatic disorders. Int J Mol Sci. MDPI AG. 2018;19(9). doi:10.3390/ijms19092783
- 24. Ding JY, Chen MJ, Wu LF, et al. Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges. Mil Med Res. BioMed Central Ltd. 2023;10(1). doi:10.1186/s40779-023-00472-w
- 25. Kim J, Kim EH, Lee H, Sung JH, Bang OY. Clinical-Scale Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Wound Healing. Int J Mol Sci. 2023;24(5). doi:10.3390/ijms24054273
- 26. Chircov C, Mihai Grumezescu A, Everard Bejenaru L. R RE EV VI IE EW W Hyaluronic acid-based scaffolds for tissue engineering. Rom J Morphol Embryol. 2018;59(1):71-76. http://www.rjme.ro/
- 27. Edye ME, Lopez-Castejon G, Allan SM, Brough D. Acidosis drives damage-associated molecular pattern (DAMP)-induced interleukin-1 secretion via a caspase-1-independent pathway. Journal of Biological Chemistry. Published online 2013. doi:10.1074/jbc.M113.478941
- 28. Seol JE, Ahn SW, Seol B, et al. Echinochrome a protects against ultraviolet b-induced photoaging by lowering collagen degradation and inflammatory cell infiltration in hairless mice. Mar Drugs. 2021;19(10). doi:10.3390/md19100550
- 29. Pandey VK, Tripathi A, Srivastava S, et al. Exploiting the bioactive properties of essential oils and their potential applications in food industry. Food Sci Biotechnol. The Korean Society of Food Science and Technology. 2023;32(7):885-902. doi:10.1007/s10068-023-01287-0
- 30. Schuster N, Krieglstein K. Mechanisms of TGF-β-mediated apoptosis. Cell Tissue Res. Preprint posted online 2002. doi:10.1007/s00441-001-0479-6
- 31. Nanashima N, Horie K, Maeda H, Tomisawa T, Kitajima M, Nakamura T. Blackcurrant anthocyanins increase the levels of collagen, elastin, and hyaluronic acid in human skin fibroblasts and ovariectomized rats. Nutrients. 2018;10(4). doi:10.3390/nu10040495
- 32. An Y, Liu WJ, Xue P. Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion. Published online 2018. doi:10.1038/s41419-017-0082-8
- 33. 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
- 34. Chircov C, Grumezescu AM, Bejenaru LE. Hyaluronic acid-based scaffolds for tissue engineering. Romanian Journal of Morphology and Embryology. Preprint posted online 2018.
How to Cite This
Copyright and Permissions

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Publishing your paper with Jurnal Teknologi Laboratorium (JTL) means that the author or authors retain the copyright in the paper. JTL granted an exclusive reuse license by the author(s), but the author(s) are able to put the paper onto a website, distribute it to colleagues, give it to students, use it in your thesis etc, even commercially. The author(s) can reuse the figures and tables and other information contained in their paper published by JTL in future papers or work without having to ask anyone for permission, provided that the figures, tables or other information that is included in the new paper or work properly references the published paper as the source of the figures, tables or other information, and the new paper or work is not direct at private monetary gain or commercial advantage.
JTL journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge. This journal is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. This license lets others remix, transform, and build upon the material for any purpose, even commercially.
JTL journal Open Access articles are distributed under this Creative Commons Attribution-ShareAlike 4.0 International License (CC BY-SA). Articles can be read and shared for All purposes under the following conditions:
- BY: You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- SA: If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original.
