Platelet-Derived Mitochondria Attenuate 5-FU-Induced Injury to Bone-Associated Mesenchymal Stem Cells

Chen, Yutong; Liu, Zhixin; Zhang, Jing; Meng, Weicheng; Wang, Wenting; Wu, Xiaoshuang; Hu, Xingbin; Chen, Yaozhen; Yin, Wen

doi:10.1155/2023/7482546

Cited by 3 publications

(1 citation statement)

References 67 publications

(87 reference statements)

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“…However, under certain types of stress, including nutritional nutrient starvation and oxidative stress, cells may adaptively elongate mitochondria through mitochondrial fusion to dilute damaged mitochondrial proteins and enhance energetic efficiency [ 61 , 62 ]. Several other studies have also observed mitochondrial elongation, along with active mitochondrial fission and fusion, which were associated with the maintenance of mitochondrial health and resistance to dysfunction [ 63 , 64 ]. Therefore, we speculated that mitochondrial elongation corresponded to an event of fusion-dominated mitochondrial dynamic changes in ESCs, adapting to the energy shortages caused by TGF-β1 mediated mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

Chen,

Ye,

Huang

et al. 2024

Biol Res

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Background Endometrial fibrosis, a significant characteristic of intrauterine adhesion (IUA), is caused by the excessive differentiation and activation of endometrial stromal cells (ESCs). Glutaminolysis is the metabolic process of glutamine (Gln), which has been implicated in multiple types of organ fibrosis. So far, little is known about whether glutaminolysis plays a role in endometrial fibrosis. Methods The activation model of ESCs was constructed by TGF-β1, followed by RNA-sequencing analysis. Changes in glutaminase1 (GLS1) expression at RNA and protein levels in activated ESCs were verified experimentally. Human IUA samples were collected to verify GLS1 expression in endometrial fibrosis. GLS1 inhibitor and glutamine deprivation were applied to ESCs models to investigate the biological functions and mechanisms of glutaminolysis in ESCs activation. The IUA mice model was established to explore the effect of glutaminolysis inhibition on endometrial fibrosis. Results We found that GLS1 expression was significantly increased in activated ESCs models and fibrotic endometrium. Glutaminolysis inhibition by GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES or glutamine deprivation treatment suppressed the expression of two fibrotic markers, α-SMA and collagen I, as well as the mitochondrial function and mTORC1 signaling in ESCs. Furthermore, inhibition of the mTORC1 signaling pathway by rapamycin suppressed ESCs activation. In IUA mice models, BPTES treatment significantly ameliorated endometrial fibrosis and improved pregnancy outcomes. Conclusion Glutaminolysis and glutaminolysis-associated mTOR signaling play a role in the activation of ESCs and the pathogenesis of endometrial fibrosis through regulating mitochondrial function. Glutaminolysis inhibition suppresses the activation of ESCs, which might be a novel therapeutic strategy for IUA.

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Section: Discussionmentioning

confidence: 99%

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

Chen,

Ye,

Huang

et al. 2024

Biol Res

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Ganoderma spore lipid ameliorates docetaxel, cisplatin, and 5-fluorouracil chemotherapy-induced damage to bone marrow mesenchymal stem cells and hematopoiesis

Lin,

Chung,

Sun

et al. 2024

BMC Complement Med Ther

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Background A triplet chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) is used to treat head and neck squamous cell carcinoma; however, it is toxic to bone marrow mesenchymal stem cells (BMSCs). We previously demonstrated that Ganoderma spore lipid (GSL) protect BMSCs against cyclophosphamide toxicity. In this study, we investigated the protective effects of GSL against TPF-induced BMSCs and hematopoietic damage. Methods BMSCs and C57BL/6 mice were divided into control, TPF, co-treatment (simultaneously treated with GSL and TPF for 2 days), and pre-treatment (treated with GSL for 7 days before 2 days of TPF treatment) groups. In vitro, morphology, phenotype, proliferation, senescence, apoptosis, reactive oxygen species (ROS), and differentiation of BMSCs were evaluated. In vivo, peripheral platelets (PLTs) and white blood cells (WBCs) from mouse venous blood were quantified. Bone marrow cells were isolated for hematopoietic colony-forming examination. Results In vitro, GSL significantly alleviated TPF-induced damage to BMSCs compared with the TPF group, recovering their morphology, phenotype, proliferation, and differentiation capacity (p < 0.05). Annexin V/PI and senescence-associated β-galactosidase staining showed that GSL inhibited apoptosis and delayed senescence in TPF-treated BMSCs (p < 0.05). GSL downregulated the expression of caspase-3 and reduced ROS formation (p < 0.05). In vivo, GSL restored the number of peripheral PLTs and WBCs and protected the colony-forming capacity of bone marrow cells (p < 0.05). Conclusions GSL efficiently protected BMSCs from damage caused by TPF and recovered hematopoiesis.

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Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Cancer

Anderson

2023

CTMC

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Platelets have traditionally been investigated for their role in clot formation in the course of cardiovascular diseases and strokes. However, recent work indicates platelets to be an integral aspect of wider systemic processes, with relevance to the pathophysiology of a host of diverse medical conditions, including neurodegenerative disorders and cancer. This article reviews platelet function and interactions with the gut microbiome and circadian systems, highlighting the role of the platelet mitochondrial melatonergic pathway in determining platelet activation, fluxes and plasticity. This provides a number of novel conceptualizations of platelet function and mode of interaction with other cell types, including the pathoetiology and pathophysiology of diverse medical conditions, such as cancer, Alzheimer’s disease, and amyotrophic lateral sclerosis. It is proposed that a platelet-gut axis allows platelets to contribute to many of the pathophysiological processes linked to gut dysbiosis and gut permeability. This is at least partly via platelet sphingosine- 1-phosphate release, which regulates enteric glial cells and lymphocyte chemotaxis, indicating an etiological role for platelets in a wide array of medical conditions linked to alterations in the gut microbiome. Platelets are also an important regulator of the various microenvironments that underpin most human medical conditions, including the tumor microenvironment, neurodegenerative diseases, and autoimmune disorders. Platelet serotonin release regulates the availability of the mitochondrial melatonergic pathway systemically, thereby being an important determinant of the dynamic metabolic interactions occurring across cell types that underpin the pathoetiology of many medical conditions. In addition, a number of novel and diverse future research directions and treatment implications are proposed.

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Platelet-Derived Mitochondria Attenuate 5-FU-Induced Injury to Bone-Associated Mesenchymal Stem Cells

Cited by 3 publications

References 67 publications

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function

Ganoderma spore lipid ameliorates docetaxel, cisplatin, and 5-fluorouracil chemotherapy-induced damage to bone marrow mesenchymal stem cells and hematopoiesis

Gut Microbiome and Circadian Interactions with Platelets Across Human Diseases, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Cancer

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