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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Jin, Yi, et al.
(författare)
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Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis
- 2022
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590. ; 1:12, s. 1156-1173
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src deficiency, VE-cadherin internalization is maintained and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity.
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| 3. |
- Miguel, Andreia, et al.
(författare)
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The SHORT-ROOT-like gene PtSHR2B is involved in Populus phellogen activity
- 2016
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Ingår i: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 67:5, s. 1545-1555
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Tidskriftsartikel (refereegranskat)abstract
- SHORT-ROOT (SHR) is a GRAS transcription factor first characterized for its role in the specification of the stem cell niche and radial patterning in Arabidopsis thaliana (At) roots. Three SHR-like genes have been identified in Populus trichocarpa (Pt). PtSHR1 shares high similarity with AtSHR over the entire length of the coding sequence. The two other Populus SHR-like genes, PtSHR2A and PtSHR2B, are shorter in their 5' ends when compared with AtSHR. Unlike PtSHR1, that is expressed throughout the cambial zone of greenhouse-grown Populus trees, PtSHR2Bprom:uidA expression was detected in the phellogen. Additionally, PtSHR1 and PtSHR2B expression patterns markedly differ in the shoot apex and roots of in vitro plants. Transgenic hybrid aspen expressing PtSHR2B under the 35S constitutive promoter showed overall reduced tree growth while the proportion of bark increased relative to the wood. Reverse transcription-quantitative PCR (RT-qPCR) revealed increased transcript levels of cytokinin metabolism and response-related genes in the transgenic plants consistent with an increase of total cytokinin levels. This was confirmed by cytokinin quantification by LC-MS/MS. Our results indicate that PtSHR2B appears to function in the phellogen and therefore in the regulation of phellem and periderm formation, possibly acting through modulation of cytokinin homeostasis. Furthermore, this work points to a functional diversification of SHR after the divergence of the Populus and Arabidopsis lineages. This finding may contribute to selection and breeding strategies of cork oak in which, unlike Populus, the phellogen is active throughout the entire tree lifespan, being at the basis of a highly profitable cork industry.
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| 4. |
- Milhinhos, Ana, et al.
(författare)
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Thermospermine levels are controlled by an auxin-dependent feedback loop mechanism in Populus xylem
- 2013
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Ingår i: The Plant Journal. - : Wiley. - 0960-7412 .- 1365-313X. ; 75:4, s. 685-698
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Tidskriftsartikel (refereegranskat)abstract
- Polyamines are small polycationic amines that are widespread in living organisms. Thermospermine, synthesized by thermospermine synthase ACAULIS5 (ACL5), was recently shown to be an endogenous plant polyamine. Thermospermine is critical for proper vascular development and xylem cell specification, but it is not known how thermospermine homeostasis is controlled in the xylem. We present data in the Populus model system supporting the existence of a negative feedback control of thermospermine levels in stem xylem tissues, the main site of thermospermine biosynthesis. While over-expression of the ACL5 homologue in Populus, POPACAULIS5, resulted in strong up-regulation of ACL5 expression and thermospermine accumulation in leaves, the corresponding levels in the secondary xylem tissues of the stem were similar or lower than those in the wild-type. POPACAULIS5 over-expression had a negative effect on accumulation of indole-3-acetic acid, while exogenous auxin had a positive effect on POPACAULIS5 expression, thus promoting thermospermine accumulation. Further, over-expression of POPACAULIS5 negatively affected expression of the classIII homeodomain leucine zipper (HD-ZipIII) transcription factor gene PttHB8, a homologue of AtHB8, while up-regulation of PttHB8 positively affected POPACAULIS5 expression. These results indicate that excessive accumulation of thermospermine is prevented by a negative feedback control of POPACAULIS5 transcript levels through suppression of indole-3-acetic acid levels, and that PttHB8 is involved in the control of POPACAULIS5 expression. We propose that this negative feedback loop functions to maintain steady-state levels of thermospermine, which is required for proper xylem development, and that it is dependent on the presence of high concentrations of endogenous indole-3-acetic acid, such as those present in the secondary xylem tissues.
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| 5. |
- González-King, Hernán, et al.
(författare)
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Head-to-head comparison of relevant cell sources of small extracellular vesicles for cardiac repair : Superiority of embryonic stem cells
- 2024
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Ingår i: Journal of Extracellular Vesicles. - : John Wiley & Sons. - 2001-3078. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) exhibited the best pro-angiogenic and anti-fibrotic effects in vitro. Then, we evaluated the functionality of the sEV with the most promising performances in vitro, in a murine model of MI-reperfusion injury (IRI) and analysed their RNA and protein compositions. In vivo, ESC-sEV provided the most favourable outcome after MI by reducing adverse cardiac remodelling through down-regulating fibrosis and increasing angiogenesis. Furthermore, transcriptomic, and proteomic characterizations of sEV derived from hTERT-MSC, ESC, and CPC revealed factors in ESC-sEV that potentially drove the observed functions. In conclusion, ESC-sEV holds great promise as a cell-free treatment for promoting cardiac repair following MI.
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