Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs
Periodontal ligament derived stem cells (PDLSC) are adult multipotent mesenchymal-like stem cells (MSCs) that can induce a promising immunomodulation to interact with immune cells for disease treatment. Metabolic reconfiguration has been shown to be involved in the immunomodulatory activity of MSCs....
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/4038 |
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| author | Payal Arora Wen Li Xiaobin Huang Wenjing Yu Ranran Huang Qian Jiang Chider Chen |
| author_facet | Payal Arora Wen Li Xiaobin Huang Wenjing Yu Ranran Huang Qian Jiang Chider Chen |
| author_sort | Payal Arora |
| collection | DOAJ |
| description | Periodontal ligament derived stem cells (PDLSC) are adult multipotent mesenchymal-like stem cells (MSCs) that can induce a promising immunomodulation to interact with immune cells for disease treatment. Metabolic reconfiguration has been shown to be involved in the immunomodulatory activity of MSCs. However, the underlying mechanisms are largely unknown, and it remains a challenging to establish a therapeutic avenue to enhance immunomodulation of endogenous stem cells for disease management. In the present study, RNA-sequencing (RNA-seq) analysis explores that curcumin significantly promotes PDLSC function through activation of MSC-related markers and metabolic pathways. In vitro stem cell characterization further confirms that self-renewal and multipotent differentiation capabilities are largely elevated in curcumin treated PDLSCs. Mechanistically, RNA-seq reveals that curcumin activates ERK and mTOR cascades through upregulating growth factor pathways for metabolic reconfiguration toward glycolysis. Interestingly, PDLSCs immunomodulation is significantly increased after curcumin treatment through activation of prostaglandin E2-Indoleamine 2,3 dioxygenase (PGE2-IDO) signaling, whereas inhibition of glycolysis activity by 2-deoxyglucose (2-DG) largely blocked immunomodulatory capacity of PDLSCs. Taken together, this study provides a novel pharmacological approach to activate endogenous stem cells through metabolic reprogramming for immunomodulation and tissue regeneration. |
| first_indexed | 2024-03-09T11:44:59Z |
| format | Article |
| id | doaj.art-f09228f0e350409c8cedc48af3c9d2e6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:44:59Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f09228f0e350409c8cedc48af3c9d2e62023-11-30T23:25:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01237403810.3390/ijms23074038Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCsPayal Arora0Wen Li1Xiaobin Huang2Wenjing Yu3Ranran Huang4Qian Jiang5Chider Chen6Early-Research Oral Care, Colgate-Palmolive Company, Piscataway, NJ 08854, USADepartment of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAPeriodontal ligament derived stem cells (PDLSC) are adult multipotent mesenchymal-like stem cells (MSCs) that can induce a promising immunomodulation to interact with immune cells for disease treatment. Metabolic reconfiguration has been shown to be involved in the immunomodulatory activity of MSCs. However, the underlying mechanisms are largely unknown, and it remains a challenging to establish a therapeutic avenue to enhance immunomodulation of endogenous stem cells for disease management. In the present study, RNA-sequencing (RNA-seq) analysis explores that curcumin significantly promotes PDLSC function through activation of MSC-related markers and metabolic pathways. In vitro stem cell characterization further confirms that self-renewal and multipotent differentiation capabilities are largely elevated in curcumin treated PDLSCs. Mechanistically, RNA-seq reveals that curcumin activates ERK and mTOR cascades through upregulating growth factor pathways for metabolic reconfiguration toward glycolysis. Interestingly, PDLSCs immunomodulation is significantly increased after curcumin treatment through activation of prostaglandin E2-Indoleamine 2,3 dioxygenase (PGE2-IDO) signaling, whereas inhibition of glycolysis activity by 2-deoxyglucose (2-DG) largely blocked immunomodulatory capacity of PDLSCs. Taken together, this study provides a novel pharmacological approach to activate endogenous stem cells through metabolic reprogramming for immunomodulation and tissue regeneration.https://www.mdpi.com/1422-0067/23/7/4038metabolic reconfigurationimmunomodulationperiodontal ligament derived stem cells (PDLSCs)mesenchymal stem cells (MSCs)RNA-sequencing (RNA-seq)prostaglandin E2 (PGE2) |
| spellingShingle | Payal Arora Wen Li Xiaobin Huang Wenjing Yu Ranran Huang Qian Jiang Chider Chen Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs International Journal of Molecular Sciences metabolic reconfiguration immunomodulation periodontal ligament derived stem cells (PDLSCs) mesenchymal stem cells (MSCs) RNA-sequencing (RNA-seq) prostaglandin E2 (PGE2) |
| title | Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs |
| title_full | Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs |
| title_fullStr | Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs |
| title_full_unstemmed | Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs |
| title_short | Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs |
| title_sort | metabolic reconfiguration activates stemness and immunomodulation of pdlscs |
| topic | metabolic reconfiguration immunomodulation periodontal ligament derived stem cells (PDLSCs) mesenchymal stem cells (MSCs) RNA-sequencing (RNA-seq) prostaglandin E2 (PGE2) |
| url | https://www.mdpi.com/1422-0067/23/7/4038 |
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