<scp>TFEB</scp>
            controls vascular development by regulating the proliferation of endothelial cells

Doronzo, Gabriella; Astanina, Elena; Corà, Davide; Chiabotto, Giulia; Comunanza, Valentina; Noghero, Alessio; Neri, Francesco; Puliafito, Alberto; Primo, Luca; Spampanato, Carmine; Settembre, Carmine; Ballabio, Andrea; Camussi, Giovanni; Oliviero, Salvatore; Bussolino, Federico

doi:10.15252/embj.201798250

Cited by 64 publications

(100 citation statements)

References 80 publications

(155 reference statements)

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“…Liver showed the strongest age correlation (cor=0.59) and both liver and blood exhibited the highest values from DNAmRep. This may reflect the higher proliferative capacity of cells in these samples [47,48]. Muscle also showed higher DNAmRep overall, but did not significantly increase with age.…”

Section: Discussionmentioning

confidence: 80%

Cellular aging in vitro recapitulates multi-tissue epigenetic aging in vivo

Minteer

Morselli

Meer

et al. 2020

Preprint

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Aging is known to elicit dramatic changes to DNA methylation (DNAm). However, the causes and consequences of such alterations to the epigenome remain unclear. Therefore, the utility of biomarkers of aging based on DNAm patterns will depend on our ability to link them to cellular features, such as proliferation, differentiation, transcriptional repression/activation, senescence, and transformation. Using DNAm from serially passaged mouse embryonic fibroblasts (MEFs), we developed a predictor of replication that is able to accurately predict passage number in independent sample. Our measure, termed DNAmRep, was shown to strongly increase with age when examined in multiple tissues (blood, liver, kidney, lung and adipose). Furthermore, we observed replicative deceleration in animal undergoing caloric restriction. Upon reprogramming to iPSCs, cells derived from both lung and kidney fibroblasts exhibited resetting of our DNAmRep measure. This measure also increased in response to differentiation among B-cell populations. Enrichment analysis implicated CBX7, RNF2 and HDAC2 as potentially important transcription factors and chromatin regulators in the DNAm replication signature. Finally, DNAmRep correlated with beta-galactosidase activity in replicative senescent MEFs, but not in radiation or drug induced senescent MEFs, and was partially separated by immortalization with Large T antigen K1 mutant (LTK1), suggesting that it reflects mitotic history, rather than senescent state. Overall, this study identifies mitotically-derived alterations to the methylome, which partially underlie known epigenetic aging phenomena.

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Section: Discussionmentioning

confidence: 80%

Cellular aging in vitro recapitulates multi-tissue epigenetic aging in vivo

Minteer

Morselli

Meer

et al. 2020

Preprint

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“…Then, we found that one of the major regulators of p21, the tumor suppressor p53 [16,27,28,[42][43][44], is required for TFEB-mediated elevation of p21. Interestingly, a residual but significant activation of p21 was observed upon the overexpression of TFEB in p53 depleted background.…”

Section: Discussionmentioning

confidence: 97%

“…Thus, TFE3 and TFEB contribute to sustaining p53-dependent response by stabilizing p53 protein levels [26]. Furthermore, TFEB depletion halts proliferation at the G1-S transition by inhibiting the CDK4/Rb pathway [27].…”

Section: Introductionmentioning

confidence: 99%

TFEB Modulates p21/WAF1/CIP1 during the DNA Damage Response

Pisonero-Vaquero

Soldati

Cesana

et al. 2020

Cells

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The MiT/TFE family of transcription factors (MITF, TFE3, and TFEB), which control transcriptional programs for autophagy and lysosome biogenesis have emerged as regulators of energy metabolism in cancer. Thus, their activation increases lysosomal catabolic function to sustain cancer cell growth and survival in stress conditions. Here, we found that TFEB depletion dramatically reduces basal expression levels of the cyclin-dependent kinase (CDK) inhibitor p21/WAF1 in various cell types. Conversely, TFEB overexpression increases p21 in a p53-dependent manner. Furthermore, induction of DNA damage using doxorubicin induces TFEB-mediated activation of p21, delays G2/M phase arrest, and promotes cell survival. Pharmacological inhibition of p21, instead, abrogates TFEB-mediated protection during the DNA damage response. Together, our findings uncover a novel and direct role of TFEB in the regulation of p21 expression in both steady-state conditions and during the induction of DNA-damage response (DDR). Our observations might open novel therapeutic strategies to promote cancer cell death by targeting the TFEB-p21 pathway in the presence of genotoxic agents.

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“…Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. TFEB promotes endothelial cell proliferation by activating the autophagic flux and regulating the G1-S transition, which is conducive to angiogenesis [141,142]. In addition, the metabolites of autophagic lysosomes can be recycled into amino acids and lipids to produce adenosine triphosphate [143], which is also one of the mechanisms of endothelial cell proliferation mentioned above.…”

Section: Inducing Autophagymentioning

confidence: 99%

Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications

Liu

Zhang

et al. 2020

J Nanobiotechnol

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The vascular system, which transports oxygen and nutrients, plays an important role in wound healing, cardiovascular disease treatment and bone tissue engineering. Angiogenesis is a complex and delicate regulatory process. Vascular cells, the extracellular matrix (ECM) and angiogenic factors are indispensable in the promotion of lumen formation and vascular maturation to support blood flow. However, the addition of growth factors or proteins involved in proangiogenic effects is not effective for regulating angiogenesis in different microenvironments. The construction of biomaterial scaffolds to achieve optimal growth conditions and earlier vascularization is undoubtedly one of the most important considerations and major challenges among engineering strategies. Nanomaterials have attracted much attention in biomedical applications due to their structure and unique photoelectric and catalytic properties. Nanomaterials not only serve as carriers that effectively deliver factors such as angiogenesis-related proteins and mRNA but also simulate the nano-topological structure of the primary ECM of blood vessels and stimulate the gene expression of angiogenic effects facilitating angiogenesis. Therefore, the introduction of nanomaterials to promote angiogenesis is a great helpful to the success of tissue regeneration and some ischaemic diseases. This review focuses on the angiogenic effects of nanoscaffolds in different types of tissue regeneration and discusses the influencing factors as well as possible related mechanisms of nanomaterials in endothelial neovascularization. It contributes novel insights into the design and development of novel nanomaterials for vascularization and therapeutic applications.

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TFEB controls vascular development by regulating the proliferation of endothelial cells

Cited by 64 publications

References 80 publications

Cellular aging in vitro recapitulates multi-tissue epigenetic aging in vivo

Cellular aging in vitro recapitulates multi-tissue epigenetic aging in vivo

TFEB Modulates p21/WAF1/CIP1 during the DNA Damage Response

Insights into the angiogenic effects of nanomaterials: mechanisms involved and potential applications

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