Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs.
Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs.
复制标题
代谢重构激活PDLSC的干细胞和免疫调节。
DOI：
10.3390/ijms23074038
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发表时间：
2022-04-06
影响因子：
5.6
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Arora P;Li W;Huang X;Yu W;Huang R;Jiang Q;Chen C
牙周膜来源干细胞(PDLSC)是一种成体多能间充质样干细胞(MSCs)，具有免疫调节功能，可与免疫细胞相互作用，用于疾病治疗。代谢重构已被证明与MSCs的免疫调节活性有关。然而，潜在的机制在很大程度上还不清楚，建立一种治疗途径来增强内源性干细胞的免疫调节用于疾病管理仍然是一个挑战。在本研究中，RNA测序(RNA-seq)分析发现，姜黄素通过激活MSC相关标志物和代谢途径显著促进PDLSC的功能。体外干细胞特性进一步证实，姜黄素处理的PDLSCs的自我更新和多潜能分化能力大大提高。从机制上讲，RNA-seq揭示了姜黄素通过上调生长因子途径来激活ERK和mTOR级联反应，以进行糖酵解的代谢重组。有趣的是，姜黄素通过激活前列腺素E2-吲哚胺2，3-双加氧酶(PGE2-IDO)信号通路显著增强了PDLSCs的免疫调节能力，而2-脱氧葡萄糖(2-DG)抑制糖酵解活性在很大程度上阻断了PDLSCs的免疫调节能力。综上所述，这项研究提供了一种新的药理学方法，通过代谢重新编程激活内源性干细胞，以进行免疫调节和组织再生。
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.
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DOI：
10.3390/molecules191220091
发表时间：
2014-12-01
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Priyadarsini KI
通讯作者：
Priyadarsini KI
影响因子：
7.3
作者：
Planat-Benard V;Varin A;Casteilla L
通讯作者：
Casteilla L
影响因子：
3.7
作者：
Olynik BM;Rastegar M
通讯作者：
Rastegar M
影响因子：
6.2
作者：
FRIEDENSTEIN, AJ;CHAILAKHYAN, RK;KEILISSB.IV
通讯作者：
KEILISSB.IV
DOI：
10.1084/jem.20140643
发表时间：
2015-01-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen C;Akiyama K;Wang D;Xu X;Li B;Moshaverinia A;Brombacher F;Sun L;Shi S
通讯作者：
Shi S