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- Hellström, Mats, et al.
(författare)
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Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis.
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 445:7129, s. 776-80
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Tidskriftsartikel (refereegranskat)abstract
- In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascular endothelial growth factor (VEGF)-A. VEGF-A is also essential for the induction of endothelial tip cells, but it is not known how single tip cells are selected to lead each vessel sprout, and how tip-cell numbers are determined. Here we present evidence that delta-like 4 (Dll4)-Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina. We show that inhibition of Notch signalling using gamma-secretase inhibitors, genetic inactivation of one allele of the endothelial Notch ligand Dll4, or endothelial-specific genetic deletion of Notch1, all promote increased numbers of tip cells. Conversely, activation of Notch by a soluble jagged1 peptide leads to fewer tip cells and vessel branches. Dll4 and reporters of Notch signalling are distributed in a mosaic pattern among endothelial cells of actively sprouting retinal vessels. At this location, Notch1-deleted endothelial cells preferentially assume tip-cell characteristics. Together, our results suggest that Dll4-Notch1 signalling between the endothelial cells within the angiogenic sprout serves to restrict tip-cell formation in response to VEGF, thereby establishing the adequate ratio between tip and stalk cells required for correct sprouting and branching patterns. This model offers an explanation for the dose-dependency and haploinsufficiency of the Dll4 gene, and indicates that modulators of Dll4 or Notch signalling, such as gamma-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis.
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- Hu, Xuchen, et al.
(författare)
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GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients
- 2019
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Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.
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- Riera, R, et al.
(författare)
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Severe shifts of Zostera marina epifauna: Comparative study between 1997 and 2018 on the Swedish Skagerrak coast
- 2020
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 158:111434
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between bottom-up and top-down processes in coastal ecosystems has been scarcely studied so far. Temporal changes in trophic interactions of Zostera marina along the Swedish west coast are relatively well studied, with the exception of epifaunal communities. Epifauna was used as a model study to explore resource (bottom-up) or predator (top-down) regulated in a vegetated ecosystem. We conducted a 21-year comparative study (1997 and 2018) using epifauna of 19 Zostera marina meadows along the Swedish Skagerrak coast. Large changes were observed in the composition of small (0.2–1 mm) and large (> 1 mm) epifauna. In the small-sized epifauna, the nematode Southernia zosterae and harpacticoids showed an increase of 90% and a decrease of 50% of their abundances, respectively. In the large-sized epifauna, the polychaete Platynereis dumerilii and chironomid larvae were absent in 1997 but thrived in 2018 (> 2000 ind. m−2). Mesoherbivores (Idoteids and gammarids) were locally very abundant in 1997 but disappeared in 2018. An 83% decline of mytilids settling in Zostera marina leaves was observed. Our results showed that epifauna is predominantly top-down regulated. An in- tegrative framework of the study area is outlined to shed light on the causes and consequences of the en- vironmental shifts reported in Zostera meadows from the northern Skagerrak area throughout the last three decades.
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