Notch and Senescence

Hoare, Matthew; Narita, Masashi

doi:10.1007/978-3-319-89512-3_15

Cited by 15 publications

(12 citation statements)

References 118 publications

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“…Notch is a single-pass transmembrane cell surface receptor that plays a critical role in cell fate via regulating differentiation and apoptosis 37 . Recent data point to a role for the Notch pathway in the dynamic control of both SASP composition and its net functional output; 38 for example, pharmacological inhibition of Notch signaling is able to reduce senescence features in esophageal keratinocytes 39 . JAG1 is a canonical Notch ligand that is remarkably increased during OA development, 40 and the JAG1-mediated Notch pathway is initiated when JAG1 binds to receptors.…”

Section: Discussionmentioning

confidence: 99%

miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

Yang

et al. 2020

Molecular Therapy - Nucleic Acids

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Osteoarthritis (OA) is a major cause of joint pain and disability, and chondrocyte senescence is a key pathological process in OA and may be a target of new therapeutics. MicroRNA-140 (miR-140) plays a protective role in OA, but little is known about its epigenetic effect on chondrocyte senescence. In this study, we first validated the features of chondrocyte senescence characterized by increased cell cycle arrest in the G0/G1 phase and the expression of senescence-associated β-galactosidase (SA-βGal), p16INK4a, p21, p53, and γH2AX in human knee OA. Then, we revealed in interleukin 1β (IL-1β)-induced OA chondrocytes in vitro that pretransfection with miR-140 effectively inhibited the expression of SA-βGal, p16INK4a, p21, p53, and γH2AX. Furthermore, in vivo results from trauma-induced early-stage OA rats showed that intra-articularly injected miR-140 could rapidly reach the chondrocyte cytoplasm and induce molecular changes similar to the in vitro results, resulting in a noticeable alleviation of OA progression. Finally, bioinformatics analysis predicted the potential targets of miR-140 and a mechanistic network by which miR-140 regulates chondrocyte senescence. Collectively, miR-140 can effectively attenuate the progression of early-stage OA by retarding chondrocyte senescence, contributing new evidence of the involvement of miR-mediated epigenetic regulation of chondrocyte senescence in OA pathogenesis.

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Section: Discussionmentioning

confidence: 99%

miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

Yang

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Interestingly, a "bystander effect" is found with cellular senescence in which paracrine factors can induce neighboring cells to undergo cellular senescence [190][191][192]. Notch signaling can also promote the transfer of the senescent phenotype, which makes one posit if Notch activation in IPF may be perpetuating cell senescence in neighboring cells [193][194][195]. Extracellular vesicles (EVs) are released from cells and carry a number of factors including proteins, nucleic acids, and lipids as cargo that can be delivered to distal cells as a means of intercellular communication [196].…”

Section: The Senescence-associated Secretory Phenotype Has Pro-fibrotmentioning

confidence: 99%

Alveolar Epithelial Type II Cells as Drivers of Lung Fibrosis in Idiopathic Pulmonary Fibrosis

Parimon

Yao

Stripp

et al. 2020

IJMS

243

172

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: Alveolar epithelial type II cells (AT2) are a heterogeneous population that have critical secretory and regenerative roles in the alveolus to maintain lung homeostasis. However, impairment to their normal functional capacity and development of a pro-fibrotic phenotype has been demonstrated to contribute to the development of idiopathic pulmonary fibrosis (IPF). A number of factors contribute to AT2 death and dysfunction. As a mucosal surface, AT2 cells are exposed to environmental stresses that can have lasting effects that contribute to fibrogenesis. Genetical risks have also been identified that can cause AT2 impairment and the development of lung fibrosis. Furthermore, aging is a final factor that adds to the pathogenic changes in AT2 cells. Here, we will discuss the homeostatic role of AT2 cells and the studies that have recently defined the heterogeneity of this population of cells. Furthermore, we will review the mechanisms of AT2 death and dysfunction in the context of lung fibrosis.

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“…In contrast to the regulation of organ size by the Hippo pathway ( Yu et al, 2015 ), Notch signaling regulates the exquisite timing and spatial programming in the organ plan, including the spatiotemporal specification of cell fate and cell differentiation, tissue patterning, and the maintenance of stem cells ( Artavanis-Tsakonas et al, 1999 ; Lasky and Wu, 2005 ; Sirin and Susztak, 2012 ; Kessler et al, 2015 ; Teo et al, 2019 ). Notch signaling is also associated with a neurological disorder, inflammation, senescence, aging, tumorigenicity, cancer drug resistance, cancer metastasis, cancer stemness, and cancer immune evasion ( Sharma et al, 2011 ; Liu et al, 2012 ; Wang et al, 2014c ; Balistreri et al, 2016 ; Hoare and Narita, 2018 ; Wu et al, 2018 ; Liu et al, 2021a ; Xiu et al, 2021 ). YAP/TAZ forms a complex with the Notch effector, Notch intracellular domain (NICD), to promote the transcription of Notch target genes ( Manderfield et al, 2012 ).…”

Section: Main Textmentioning

confidence: 99%

Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis

Guo

2022

Front. Cell Dev. Biol.

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Organ development, homeostasis, and repair often rely on bidirectional, self-organized cell-niche interactions, through which cells select cell fate, such as stem cell self-renewal and differentiation. The niche contains multiplexed chemical and mechanical factors. How cells interpret niche structural information such as the 3D topology of organs and integrate with multiplexed mechano-chemical signals is an open and active research field. Among all the niche factors, reactive oxygen species (ROS) have recently gained growing interest. Once considered harmful, ROS are now recognized as an important niche factor in the regulation of tissue mechanics and topology through, for example, the HIF-YAP-Notch signaling pathways. These pathways are not only involved in the regulation of stem cell physiology but also associated with inflammation, neurological disorder, aging, tumorigenesis, and the regulation of the immune checkpoint molecule PD-L1. Positive feedback circuits have been identified in the interplay of ROS and HIF-YAP-Notch signaling, leading to the possibility that under aberrant conditions, self-organized, ROS-dependent physiological regulations can be switched to self-perpetuating dysregulation, making ROS a double-edged sword at the interface of stem cell physiology and tumorigenesis. In this review, we discuss the recent findings on how ROS and tissue mechanics affect YAP-HIF-Notch-PD-L1 signaling, hoping that the knowledge can be used to design strategies for stem cell-based and ROS-targeting therapy and tissue engineering.

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Notch and Senescence

Cited by 15 publications

References 118 publications

miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

Alveolar Epithelial Type II Cells as Drivers of Lung Fibrosis in Idiopathic Pulmonary Fibrosis

Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis

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