Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells
Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therape...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3367 |
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| author | Rocío Mato-Basalo Miriam Morente-López Onno J Arntz Fons A. J. van de Loo Juan Fafián-Labora María C. Arufe |
| author_facet | Rocío Mato-Basalo Miriam Morente-López Onno J Arntz Fons A. J. van de Loo Juan Fafián-Labora María C. Arufe |
| author_sort | Rocío Mato-Basalo |
| collection | DOAJ |
| description | Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature. |
| first_indexed | 2024-03-10T12:55:19Z |
| format | Article |
| id | doaj.art-9e69c9545c8447e498683ac6ef82eca2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:55:19Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9e69c9545c8447e498683ac6ef82eca22023-11-21T11:58:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227336710.3390/ijms22073367Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem CellsRocío Mato-Basalo0Miriam Morente-López1Onno J Arntz2Fons A. J. van de Loo3Juan Fafián-Labora4María C. Arufe5Grupo de Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Ciencias Biomédicas y Medicina, Universdidade da Coruña, 15006 A Coruña, SpainGrupo de Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Ciencias Biomédicas y Medicina, Universdidade da Coruña, 15006 A Coruña, SpainExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsExperimental Rheumatology, Department of Rheumatology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsGrupo de Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Ciencias Biomédicas y Medicina, Universdidade da Coruña, 15006 A Coruña, SpainGrupo de Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Ciencias Biomédicas y Medicina, Universdidade da Coruña, 15006 A Coruña, SpainMesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.https://www.mdpi.com/1422-0067/22/7/3367mesenchymal stem cellsinflamm-agingcellular senescenceSASPsEV |
| spellingShingle | Rocío Mato-Basalo Miriam Morente-López Onno J Arntz Fons A. J. van de Loo Juan Fafián-Labora María C. Arufe Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells International Journal of Molecular Sciences mesenchymal stem cells inflamm-aging cellular senescence SASP sEV |
| title | Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells |
| title_full | Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells |
| title_fullStr | Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells |
| title_full_unstemmed | Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells |
| title_short | Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells |
| title_sort | therapeutic potential for regulation of the nuclear factor kappa b transcription factor p65 to prevent cellular senescence and activation of pro inflammatory in mesenchymal stem cells |
| topic | mesenchymal stem cells inflamm-aging cellular senescence SASP sEV |
| url | https://www.mdpi.com/1422-0067/22/7/3367 |
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