Retinal blood vessel‐origin yes‐associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF)

Ai, Liqianyu; Yuan, Rongdi; Chen, Xi; Liu, Yunjia; Liu, Wen‐Yi; Zhu, Jianwei; Zhang, Zhou; Yan, Jun; Chen, Chunlin; Lin, Sen; Ye, Jian

doi:10.1111/cpr.12757

Cited by 6 publications

(3 citation statements)

References 60 publications

(133 reference statements)

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“…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 ]. These observations further corroborate the evidence that 3D geometric disposition of the cells, and their interaction with the substrate effectively induce changes in gene expression mediated by the different action of the transcription factor YAP.…”

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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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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“…YAP has been shown to play a key role in the development of retinal blood vessels [22]. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis [23].…”

Section: Discussionmentioning

confidence: 99%

RIPC may promotes angiogenesis of myocardium by downregulation of miR-148a

Li,

Zhao,

Nie

et al. 2023

Preprint

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Angiogenesis is essential for repairing of cardiac tissue after myocardial infarction[1]. Remote ischemic preconditioning (RIPC) induced by cycles of transient limb ischemia and reperfusion is a very efficient cardioprotective strategy, which has pleiotropic effects, such as angiogenesis etc[1], [2]. Over the last decades many experimental and clinical studies have proven cardioprotective effects of RIPC, especially in the context of myocardial ischemia/reperfusion (I/R) injury[3]–[5]. However, the detailed mechanisms how RIPC works remains incomplete. Here, we report our investigation about the effects of RIPC in angiogenesis. And a possible mechanism that RIPC promotes angiogenesis by downregulation of miR-148a. In our study, RIPC downregulated miR-148a level in humans’ serum. Moreover, MicroRNA stem loop RT-PCR assays demonstrated that chronic RIPC (cRIPC) had lower expression of miR-148a than one-time RIPC. By analyzing HUVEC cells with overexpression or knockdown of miR-148a, it revealed that knockdown of miR-148a led to overexpression of ROCK1, YAP and Ang2, which also promotes angiogenesis. On the other hand, overexpression of miR-148a inhibited expression of ROCK1, YAP and Ang2. Overexpression of miR-148a also inhibited cell proliferation, migration, and tube formation of HUVEC cells. In conclusion, this study reveals that downregulation of miR-148a may play important role in RIPC by promoting angiogenesis. Downregulation of miR-148a could increase the expression level of ROCK1, YAP and Ang2. ROCK1 and YAP may be involved in the pathway that knockdown or downregulation of miR-148a may enhance angiogenesis through Ang2. The results provide novel understanding of the mechanism of RIPC towards angiogenesis and effect of miR-148a in angiogenesis.

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“…A key contributor in this coupling is the oxygen supplied 512 by blood perfusion of the newly formed vessels, which converts immature astrocytes into 513 mature astrocytes (Duan et al, 2017;Duan et al, 2014;West et al, 2005), in part by promoting 514 GFAP expression, and by repressing VEGF expression, otherwise induced by hypoxia (Duan et 515 al., 2017;Duan et al, 2014;Rattner et al, 2019;West et al, 2005). Aside from oxygen, other EC-516 derived factors also contributing to astrocyte maturation include ApelinJ (Sakimoto et al, 2012) 517 or LIF (Ai et al, 2020;Mi et al, 2001). Thus, interfering with EC migration, for example by 518 exposure of the retina to VEGF signaling inhibitors (Morita et al, 2017), leads to a delay in 519 astrocyte maturation.…”

Section: Or By 483mentioning

confidence: 99%

Fat1 regulates astrocyte maturation and angiogenesis in the retina

Helmbacher

2020

Preprint

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Angiogenesis is a stepwise process leading to blood vessel formation. In the vertebrate retina, endothelial cells are guided by astrocytes migrating along the inner surface, and the two processes are coupled by a tightly regulated cross-talk between the two cell types. Here, we investigated how the FAT1 Cadherin, a regulator of tissue morphogenesis governing tissue cross-talks, influences retinal vascular development. Through late-onset inactivation in the neural lineage in mice, we bypassed an early contribution of Fat1 to eye development, and assessed its requirement for postnatal retina angiogenesis. We found that neural Fat1 expression, by controlling the polarity of astrocyte progenitor migration, regulates astrocyte maturation. By interfering with astrocyte migration and maturation, neural Fat1 deletion deregulates the astrocyte/endothelial cell coupling, and delays retinal angiogenesis. Mice with neural-Fat1 ablation exhibit persistent abnormalities of the retinal vascular architecture, such as an increased vascular density in deep layers. Altogether, this study identifies Fat1 as a regulator of neurovascular communication, essential for retinal vascular development and integrity.angiogenic factors produced by neural cells is key to orchestrate astrocyte/endothelial cell 52 coupling, hence influencing the timing and dynamics of angiogenesis. 53

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Retinal blood vessel‐origin yes‐associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF)

Cited by 6 publications

References 60 publications

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

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

RIPC may promotes angiogenesis of myocardium by downregulation of miR-148a

Fat1 regulates astrocyte maturation and angiogenesis in the retina

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