Reactive Oxygen Species, Superoxide Dimutases, and PTEN-p53-AKT-MDM2 Signaling Loop Network in Mesenchymal Stem/Stromal Cells Regulation

Matsuda, Satoru; Nakagawa, Yoshiyuki; Kitagishi, Yasuko; Nakanishi, Atsuko; Murai, Toshiyuki

doi:10.3390/cells7050036

Cited by 56 publications

(49 citation statements)

References 84 publications

(90 reference statements)

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“…Western blot results showed the same change ( Figure 2B). Then, we examined the expression of p53 and p21 during the replicative senescence of mBMSCs by continuous long-term passage [15] and found that p53 and p21 were signi cantly increased after passage 20 (P20) compared with the early phase passage 5 (P5) ( Figure 2C, 2D). It is possible to conclude that p53 and p21 were upregulated in the process of cellular senescence induced by H 2 O 2 or serial passage.…”

Section: Resultsmentioning

confidence: 99%

The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

Xia

Jiang

Wang

et al. 2020

Preprint

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Background: The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is diminished. However, little is known about the mechanisms. p53 not only regulates cellular senescence but also, as a negative regulator, is involved in bone formation. This study investigated the molecular mechanism of p53 in cellular senescence and osteogenesis.Methods: The expression of p53 and its downstream gene p21 were measured during cellular senescence and osteogenesis differentiation of primary bone marrow MSCs. Then miR-145a was picked out from those p53-induced miRNAs as its expression change in bone marrow MSCs senescence and osteogenesis induced by H2O2 and BMP-9, respectively. The function of p53 induced miR-145a was analyzed by transfected with miRNA mimic in osteogenic differentiation of MSCs. Western blot and luciferase reporter assay were used for validating the target of miR-145a. Results: p53, its downstream effector p21, and p53-induced miR-145a were significantly upregulated during primary MSCs senescence and osteogenesis. Overexpression of miR-145a promoted cellular senescence and inhibited osteogenic differentiation of MSCs. p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a on osteogenesis.Conclusions: p53-induced miR-145a functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel pathway p53/miR-145a/Cbfb in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.

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Section: Resultsmentioning

confidence: 99%

The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

Xia

Jiang

Wang

et al. 2020

Preprint

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“…While free radicals have been reported crucial for normal biology of stem cells, excessive ROS (oxidative stress) adversely influence the stem cell properties and cell therapy outcome (Matsuda, Nakagawa, Kitagishi, Nakanishi, & Murai, 2018). Therefore, it is imperative to control the extent of ROS to have a promising regenerative therapy in damaged tissue linked to hypoxia and oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is imperative to control the extent of ROS to have a promising regenerative therapy in damaged tissue linked to hypoxia and oxidative stress. Additionally, oxidative stress can affect stem cell expansion and longevity (Matsuda et al, 2018). Moreover, it may be possible to control MSCs' fate in vitro and in vivo by regulating the ROS levels surrounding MSCs.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells

Nouri

Gueguen

Saeedi

et al. 2020

Journal Cellular Physiology

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The cell therapy of damaged tissue, which is linked to hypoxia condition might fail, in large part due to the emergence of oxidative stress (OS) and/or mitochondrial dysfunctions. Thus, the invigoration of stem cells against oxidative stress could be a reliable strategy to improve the cell therapy outcome. Of various antioxidants, mito‐Tempo (mito‐T) is one of the potent antioxidants that could target and neutralize the mitochondrial oxidative stress. In this study, for the induction of hypoxia and oxidative stress in mitochondria of the mesenchymal stem cells (MSCs) isolated from human adipose tissue, antimycin A (AMA) was used and then several parameters were analyzed, including cell viability and cell cycle arrest of MSCs exposed to AMA, mito‐T, antioxidant potential, redox homeostasis, and signaling pathways in MSCs under oxidative stress. Based on our findings, the treated MSCs were found to impose a high resistance to the OS‐induced apoptosis, which correlated with the nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway required to manage OS. Upon exposure of the MSCs to high oxidative stress conditions using AMA, the cells failed to scavenge. The use of mito‐T was found to alleviate the damage induced by oxidative stress through both direct functions of the free radical scavenging and the interplay in terms of cell signaling pathways including the upregulation of the Nrf2 pathway. These findings may pave the way in the stem cell therapy for the hypoxia‐mediated tissue damage.

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“…MAPK, is an important mediator responsive to extracellular stressors [46] [47] [48]. The fact that p38 MAPK is involved in the molecular interaction during aging indicates that p53 is a major mediator of ROS-related signal transduction.…”

Section: Impact Of Stem Cell Senescence In Aging and Diseasesmentioning

confidence: 99%

Therapeutics of Stem Cell Treatment in Anti-Aging and Rejuvenation

Yeh¹,

Chan²

2018

SCD

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Aging populations are increasing the incidence of age-related diseases, resulting in problems at the individual and socioeconomic level. The need for effective strategies in regenerative medicine for the elderly is more important than ever. Previous studies have shown that the number and function of stem cells decline with age, thereby undermining endogenous repair processes. It has also been suggested that the aging-induced deterioration of stem cell function may play a key role in the pathophysiology of various aging-related diseases. Recent advances in our understanding of tissue regeneration and the development of methods aimed at inducing and differentiating pluripotent stem cells for cell replacement therapy which provides exciting opportunities for the treatment of degenerative diseases, such as those related to senility. In this review article, we examine several mechanisms that are believed to contribute to the aging-related dysfunction of stem cells associated with diseases of the immune system, cardiac tissue, neuronal system, articular cartilage, and skeletal muscle. We also discuss factors that affect the therapeutic potential of adult stem/progenitor cells as well as current trends in the treatment of these conditions using regenerative medicine.

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Reactive Oxygen Species, Superoxide Dimutases, and PTEN-p53-AKT-MDM2 Signaling Loop Network in Mesenchymal Stem/Stromal Cells Regulation

Cited by 56 publications

References 84 publications

The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells

Therapeutics of Stem Cell Treatment in Anti-Aging and Rejuvenation

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