Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate

Peterson, Amy; Ingram, Kayla; Huang, E‐Chu; Parksong, Jeeun; McKenney, Connor; Bever, Gabe S.; Regot, Sergi

doi:10.1016/j.cels.2022.10.003

Cited by 12 publications

(5 citation statements)

References 36 publications

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“…Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved intracellular serine/threonine protein kinases, mainly including p38 MAPK, extracellular signal-regulated kinases (ERKs), and c-Jun N-terminal kinases (JNKs). 48 P38, was first recognized as an environmental stress sensor and participated in the regulation of various cellular functions, including the differentiation of cells. 49 We previously reported that p38 MAPK signaling is involved in angiogenesis and bone regeneration.…”

Section: Effect Of Microgroove Patterns On Bmsc Differentiationmentioning

confidence: 99%

Microgroove Cues Guiding Fibrogenesis of Stem Cells via Intracellular Force

Lei

Miao

Wang

et al. 2023

ACS Appl. Mater. Interfaces

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Groove patterns are widely used in material surface modifications. However, the independent role of ditches/ridges in regulating fibrosis of soft tissues is not well-understood, especially the lack of linkage evidence in vitro and in vivo. Herein, two kinds of combinational microgroove chips with the gradient ditch/ridge width were fabricated by photolithography technology, termed R and G groups, respectively. In group R, the ridge width was 1, 5, 10, and 30 μm, with a ditch width of 30 μm; in group G, the groove width was 5, 10, 20, and 30 μm, and the ridge width was 5 μm. The effect of microgrooves on the morphology, proliferation, and expression of fibrous markers of stem cells was systematically investigated in vitro. Moreover, thicknesses of fibrous capsules were evaluated after chips were implanted into the muscular pouches of rats for 5 months. The results show that microgrooves have almost no effect on cell proliferation but significantly modulate the morphology of cells and focal adhesions (FAs) in vitro, as well as fibrosis differentiation. In particular, the differentiation of stem cells is attenuated after the intracellular force caused by stress fibers and FAs is interfered by drugs, such as rotenone and blebbistatin. Histological analysis shows that patterns of high intracellular force can apparently stimulate soft tissue fibrosis in vivo. This study not only reveals the specific rules and mechanisms of ditch/ridge regulating stem cell behaviors but also offers insight into tailoring implant surface patterns to induce controlled soft tissue fibrosis.

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Section: Effect Of Microgroove Patterns On Bmsc Differentiationmentioning

confidence: 99%

Microgroove Cues Guiding Fibrogenesis of Stem Cells via Intracellular Force

Lei

Miao

Wang

et al. 2023

ACS Appl. Mater. Interfaces

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“…MAPK serves as a crucial signal transmitter, relaying messages from the cell surface to the nucleus, and plays a pivotal role in regulating various essential physiological processes such as cell growth, differentiation, stress adaptation, and inflammatory response (Peterson et al., 2022). Numerous studies have demonstrated that exposure to nearly all foodborne mycotoxins can disrupt the MAPK signal cascade, leading to abnormal expression of downstream targets (Sun et al., 2022).…”

Section: The Intestinal Toxicity Mechanism Of Foodborne Mycotoxinsmentioning

confidence: 99%

Section: Mapk Signal-mediated Imbalancesmentioning

confidence: 99%

Insights into the intestinal toxicity of foodborne mycotoxins through gut microbiota: A comprehensive review

Ruan,

Huang,

Yue

et al. 2023

Comp Rev Food Sci Food Safe

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Mycotoxins, which are fungal metabolites, pose a significant global food safety concern by extensively contaminating food and feed, thereby seriously threatening public health and economic development. Many foodborne mycotoxins exhibit potent intestinal toxicity. However, the mechanisms underlying mycotoxin‐induced intestinal toxicity are diverse and complex, and effective prevention or treatment methods for this condition have not yet been established in clinical and animal husbandry practices. In recent years, there has been increasing attention to the role of gut microbiota in the occurrence and development of intestinal diseases. Hence, this review aims to provide a comprehensive summary of the intestinal toxicity mechanisms of six common foodborne mycotoxins. It also explores novel toxicity mechanisms through the “key gut microbiota–key metabolites–key targets” axis, utilizing multiomics and precision toxicology studies with a specific focus on gut microbiota. Additionally, we examine the potential beneficial effects of probiotic supplementation on mycotoxin‐induced toxicity based on initial gut microbiota‐mediated mycotoxicity. This review offers a systematic description of how mycotoxins impact gut microbiota, metabolites, and genes or proteins, providing valuable insights for subsequent toxicity studies of mycotoxins. Furthermore, it lays a theoretical foundation for preventing and treating intestinal toxicity caused by mycotoxins and advancing food safety practices.

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“…MAPKs are signal-transducing kinases that respond to various stimuli, such as mitogens and heat shock and pro-inflammatory cytokines and mediate important cell functions including gene expression, proliferation, differentiation, cell survival, and apoptosis [308,309]. MAPKs comprise three main subgroups, ERK, c-Jun amino-terminal kinases (JNK), and p38 [310]. Lanna et al observed that sestrins were expressed at a much higher level by senescent CD4 + CD28 − T cells derived from the elderly [311].…”

Section: Dysregulated Signaling Contributes To Immunosenescencementioning

confidence: 99%

Counteracting Immunosenescence—Which Therapeutic Strategies Are Promising?

2023

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Aging attenuates the overall responsiveness of the immune system to eradicate pathogens. The increased production of pro-inflammatory cytokines by innate immune cells under basal conditions, termed inflammaging, contributes to impaired innate immune responsiveness towards pathogen-mediated stimulation and limits antigen-presenting activity. Adaptive immune responses are attenuated as well due to lowered numbers of naïve lymphocytes and their impaired responsiveness towards antigen-specific stimulation. Additionally, the numbers of immunoregulatory cell types, comprising regulatory T cells and myeloid-derived suppressor cells, that inhibit the activity of innate and adaptive immune cells are elevated. This review aims to summarize our knowledge on the cellular and molecular causes of immunosenescence while also taking into account senescence effects that constitute immune evasion mechanisms in the case of chronic viral infections and cancer. For tumor therapy numerous nanoformulated drugs have been developed to overcome poor solubility of compounds and to enable cell-directed delivery in order to restore immune functions, e.g., by addressing dysregulated signaling pathways. Further, nanovaccines which efficiently address antigen-presenting cells to mount sustained anti-tumor immune responses have been clinically evaluated. Further, senolytics that selectively deplete senescent cells are being tested in a number of clinical trials. Here we discuss the potential use of such drugs to improve anti-aging therapy.

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Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate

Cited by 12 publications

References 36 publications

Microgroove Cues Guiding Fibrogenesis of Stem Cells via Intracellular Force

Microgroove Cues Guiding Fibrogenesis of Stem Cells via Intracellular Force

Insights into the intestinal toxicity of foodborne mycotoxins through gut microbiota: A comprehensive review

Counteracting Immunosenescence—Which Therapeutic Strategies Are Promising?

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