TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells

Choi, Hyun-Jung; Kim, Na Eun; Kim, Byeong Mo; Seo, Min Ji; Heo, Ji Hoe

doi:10.3390/ijms19113428

Cited by 55 publications

(47 citation statements)

References 39 publications

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“…Hippo-Yap plays important roles in regulating cell proliferation/death homeostasis and mediating tissue development or organ size 43 . It has been shown that Yap translocates to the nucleus and is activated in response to TNF-α in endothelial cells 44 . Gao et al 45 confirmed that TNF-α triggers IKK-mediated Yap activation in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

et al. 2020

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Previous studies have shown that tumor necrosis factor (TNF)-α is a mediator of hepatotoxicity in liver injury. Moreover, TNF-α has also been reported to have a protective effect in liver regeneration, yet the function of TNF-α during liver injury remains controversial. Here, we report that the concentration of TNF-α determines its functions. High concentrations of TNF-α could aggravate LPS-induced liver injury. However, the TNF-α level was unchanged during APAP-induced liver injury, which exerted a protective effect. We expected that the concentration of TNF-α may affect its function. To test this hypothesis, TNF-α −/− rats or hepatocyte cells were treated with different concentrations of TNF-α. We found low TNF-α could reduce the levels of ALT and AST in the plasma of TNF-α −/− rats and promote the proliferation of hepatocyte cells. However, the levels of ALT and AST increased gradually with increasing TNF-α concentration after reaching the lowest value. Moreover, we showed that TNF-α affects the cell proliferation and cell death of hepatocytes by regulating Yap activity. Low TNF-α promoted Yap1 nuclear translocation, triggering the proliferation of hepatocytes. However, high TNF-α triggered the phosphorylation and inactivation of Yap1, preventing its nuclear import and consequently promoting cell death. Collectively, our findings provide novel evidence that the concentration of TNF-α is an important factor affecting its function in liver injury, which may provide a reference for the clinical treatment of liver injury.

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Section: Discussionmentioning

confidence: 99%

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

et al. 2020

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“…It is of interest that among the genes that are differentially expressed by the two culture conditions we studied, some of them are regulated by YAP. In particular, Tnf, which we estimated to be downregulated in MSCs culture in the 3D Nichoid, are known to be regulated by YAP [ 51 ]. As far as genes upregulated by the 3D Nichoid, as compared to the flat surface, Lif, IL6, and BMPs are also known to be regulated by YAP [ 52 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of the 3D Artificial Nichoid on the Morphology and Mechanobiological Response of Mesenchymal Stem Cells Cultured In Vitro

Remuzzi

Bonandrini

Tironi

et al. 2020

Cells

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Stem cell fate and behavior are affected by the bidirectional communication of cells and their local microenvironment (the stem cell niche), which includes biochemical cues, as well as physical and mechanical factors. Stem cells are normally cultured in conventional two-dimensional monolayer, with a mechanical environment very different from the physiological one. Here, we compare culture of rat mesenchymal stem cells on flat culture supports and in the “Nichoid”, an innovative three-dimensional substrate micro-engineered to recapitulate the architecture of the physiological niche in vitro. Two versions of the culture substrates Nichoid (single-layered or “2D Nichoid” and multi-layered or “3D Nichoid”) were fabricated via two-photon laser polymerization in a biocompatible hybrid organic-inorganic photoresist (SZ2080). Mesenchymal stem cells, isolated from rat bone marrow, were seeded on flat substrates and on 2D and 3D Nichoid substrates and maintained in culture up to 2 weeks. During cell culture, we evaluated cell morphology, proliferation, cell motility and the expression of a panel of 89 mesenchymal stem cells’ specific genes, as well as intracellular structures organization. Our results show that mesenchymal stem cells adhered and grew in the 3D Nichoid with a comparable proliferation rate as compared to flat substrates. After seeding on flat substrates, cells displayed large and spread nucleus and cytoplasm, while cells cultured in the 3D Nichoid were spatially organized in three dimensions, with smaller and spherical nuclei. Gene expression analysis revealed the upregulation of genes related to stemness and to mesenchymal stem cells’ features in Nichoid-cultured cells, as compared to flat substrates. The observed changes in cytoskeletal organization of cells cultured on 3D Nichoids were also responsible for a different localization of the mechanotransducer transcription factor YAP, with an increase of the cytoplasmic retention in cells cultured in the 3D Nichoid. This difference could be explained by alterations in the import of transcription factors inside the nucleus due to the observed decrease of mean nuclear pore diameter, by transmission electron microscopy. Our data show that 3D distribution of cell volume has a profound effect on mesenchymal stem cells structure and on their mechanobiological response, and highlight the potential use of the 3D Nichoid substrate to strengthen the potential effects of MSC in vitro and in vivo.

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“…Upstream signaling pathways regulating YAP/TAZ activity have been shown to mediate cellular interactions with a broad range of microenvironmental factors including (i) soluble bioactive ligands ( Yu et al, 2012 ; Cai and Xu, 2013 ; Chen and Harris, 2016 ; Yang et al, 2019 ), (ii) biomechanical cues ( Dupont et al, 2011 ; Kim et al, 2011 ; Nardone et al, 2017 ; Pardo-Pastor et al, 2018 ), (iii) energy, osmotic and hypoxic stress ( DeRan et al, 2014 ; Ma et al, 2015 ; Mo et al, 2015 ), and (iv) inflammation and tissue injury ( Gregorieff et al, 2015 ; Kim H. B. et al, 2017 ; Choi et al, 2018 ; Flinn et al, 2019 ), via a diverse array of surface receptors, cytoskeletal elements and cytosolic signaling proteins, as illustrated in Figure 2 . Hence, by manipulating YAP/TAZ signaling, we can control how stem/progenitor cells change their phenotype in response to external stimulation and microenvironmental cues.…”

Section: Introductionmentioning

confidence: 99%

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

Heng

Zhang

Aubel

et al. 2020

Front. Cell Dev. Biol.

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The penultimate effectors of the Hippo signaling pathways YAP and TAZ, are transcriptional co-activator proteins that play key roles in many diverse biological processes, ranging from cell proliferation, tumorigenesis, mechanosensing and cell lineage fate determination, to wound healing and regeneration. In this review, we discuss the regulatory mechanisms by which YAP/TAZ control stem/progenitor cell differentiation into the various major lineages that are of interest to tissue engineering and regenerative medicine applications. Of particular interest is the key role of YAP/TAZ in maintaining the delicate balance between quiescence, self-renewal, proliferation and differentiation of endogenous adult stem cells within various tissues/organs during early development, normal homeostasis and regeneration/healing. Finally, we will consider how increasing knowledge of YAP/TAZ signaling might influence the trajectory of future progress in regenerative medicine.

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TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells

Cited by 55 publications

References 39 publications

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

Effect of the 3D Artificial Nichoid on the Morphology and Mechanobiological Response of Mesenchymal Stem Cells Cultured In Vitro

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

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