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The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1.
Senescent cells withdraw from the cell cycle and do not proliferate. The prevalence of senescent compared to normally functioning parenchymal cells increases with age, impairing tissue and organ homeostasis. A contentious principle governing this process has been the redox theory of aging. We linked matricellular protein thrombospondin 1 (TSP1) and its receptor CD47 to the activation of NADPH oxidase 1 (Nox1), but not of the other closely related Nox isoforms, and associated oxidative stress, and to senescence in human cells and aged tissue. In human endothelial cells, TSP1 promoted senescence and attenuated cell cycle progression and proliferation. At the molecular level, TSP1 increased Nox1-dependent generation of reactive oxygen species (ROS), leading to the increased abundance of the transcription factor p53. p53 mediated a DNA damage response that led to senescence through Rb and p21cip, both of which inhibit cell cycle progression. Nox1 inhibition blocked the ability of TSP1 to increase p53 nuclear localization and p21cip abundance and its ability to promote senescence. Mice lacking TSP1 showed decreases in ROS production, p21cip expression, p53 activity, and aging-induced senescence. Conversely, lung tissue from aging humans displayed increases in the abundance of vascular TSP1, Nox1, p53, and p21cip Finally, genetic ablation or pharmacological blockade of Nox1 in human endothelial cells attenuated TSP1-mediated ROS generation, restored cell cycle progression, and protected against senescence. Together, our results provide insights into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence and suggest potential targets for controlling the aging process at the molecular level
Relationship of Weather Types on the Seasonal and Spatial Variability of Rainfall, Runoff, and Sediment Yield in the Western Mediterranean Basin
Rainfall is the key factor to understand soil erosion processes, mechanisms, and rates. Most research was conducted to determine rainfall characteristics and their relationship with soil erosion (erosivity) but there is little information about how atmospheric patterns control soil losses, and this is important to enable sustainable environmental planning and risk prevention. We investigated the temporal and spatial variability of the relationships of rainfall, runoff, and sediment yield with atmospheric patterns (weather types, WTs) in the western Mediterranean basin. For this purpose, we analyzed a large database of rainfall events collected between 1985 and 2015 in 46 experimental plots and catchments with the aim to: (i) evaluate seasonal differences in the contribution of rainfall, runoff, and sediment yield produced by the WTs; and (ii) to analyze the seasonal efficiency of the different WTs (relation frequency and magnitude) related to rainfall, runoff, and sediment yield. The results indicate two different temporal patterns: the first weather type exhibits (during the cold period: autumn and winter) westerly flows that produce the highest rainfall, runoff, and sediment yield values throughout the territory; the second weather type exhibits easterly flows that predominate during the warm period (spring and summer) and it is located on the Mediterranean coast of the Iberian Peninsula. However, the cyclonic situations present high frequency throughout the whole year with a large influence extended around the western Mediterranean basin. Contrary, the anticyclonic situations, despite of its high frequency, do not contribute significantly to the total rainfall, runoff, and sediment (showing the lowest efficiency) because of atmospheric stability that currently characterize this atmospheric pattern. Our approach helps to better understand the relationship of WTs on the seasonal and spatial variability of rainfall, runoff and sediment yield with a regional scale based on the large dataset and number of soil erosion experimental stations.Spanish Government (Ministry of Economy and Competitiveness, MINECO) and FEDER Projects: CGL2014 52135-C3-3-R, ESP2017-89463-C3-3-R, CGL2014-59946-R, CGL2015-65569-R, CGL2015-64284-C2-2-R, CGL2015-64284-C2-1-R, CGL2016-78075-P, GL2008-02879/BTE, LEDDRA 243857, RECARE-FP7, CGL2017-83866-C3-1-R, and PCIN-2017-061/AEI. Dhais Peña-Angulo received a âJuan de la Ciervaâ postdoctoral contract (FJCI-2017-33652 Spanish Ministry of Economy and Competitiveness, MEC). Ana Lucia acknowledge the "Brigitte-Schlieben-Lange-Programm". The âGeoenvironmental Processes and Global Changeâ (E02_17R) was financed by the AragĂłn Government and the European Social Fund. JosĂ© AndrĂ©s LĂłpez-TarazĂłn acknowledges the Secretariat for Universities and Research of the Department of the Economy and Knowledge of the Autonomous Government of Catalonia for supporting the Consolidated Research Group 2014 SGR 645 (RIUS- Fluvial Dynamics Research Group). Artemi CerdĂ thank the funding of the OCDE TAD/CRP JA00088807. JosĂ© MartĂnez-Fernandez acknowledges the project Unidad de Excelencia CLU-2018-04 co-funded by FEDER and Castilla y LeĂłn Government. Ane Zabaleta is supported by the Hydro-Environmental Processes consolidated research group (IT1029-16, Basque Government). This paper has the benefit of the Lab and Field Data Pool created within the framework of the COST action CONNECTEUR (ES1306)
Relationship of weather types on the seasonal and spatial variability of rainfall, runoff, and sediment yield in the western Mediterranean basin
Rainfall is the key factor to understand soil erosion processes, mechanisms, and rates. Most research was conducted to determine rainfall characteristics and their relationship with soil erosion (erosivity) but there is little information about how atmospheric patterns control soil losses, and this is important to enable sustainable environmental planning and risk prevention. We investigated the temporal and spatial variability of the relationships of rainfall, runoff, and sediment yield with atmospheric patterns (weather types, WTs) in the western Mediterranean basin. For this purpose, we analyzed a large database of rainfall events collected between 1985 and 2015 in 46 experimental plots and catchments with the aim to: (i) evaluate seasonal differences in the contribution of rainfall, runoff, and sediment yield produced by the WTs; and (ii) to analyze the seasonal efficiency of the different WTs (relation frequency and magnitude) related to rainfall, runoff, and sediment yield. The results indicate two different temporal patterns: the first weather type exhibits (during the cold period: autumn and winter) westerly flows that produce the highest rainfall, runoff, and sediment yield values throughout the territory; the second weather type exhibits easterly flows that predominate during the warm period (spring and summer) and it is located on the Mediterranean coast of the Iberian Peninsula. However, the cyclonic situations present high frequency throughout the whole year with a large influence extended around the western Mediterranean basin. Contrary, the anticyclonic situations, despite of its high frequency, do not contribute significantly to the total rainfall, runoff, and sediment (showing the lowest efficiency) because of atmospheric stability that currently characterize this atmospheric pattern. Our approach helps to better understand the relationship of WTs on the seasonal and spatial variability of rainfall, runoff and sediment yield with a regional scale based on the large dataset and number of soil erosion experimental stations
HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction
Farmer knowledge, perception and management of soils in the Las Vegas agricultural district, Madrid, Spain
Adenosine stimulates angiogenesis by up-regulating production of thrombospondin-1 by macrophages
TSP1âCD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction
THBS1 facilitates colorectal liver metastasis through enhancing epithelialâmesenchymal transition
Spatial variability of the relationships of runoff and sediment yield with weather types throughout the Mediterranean basin
Soil degradation by water is a serious environmental problem worldwide, with specific climatic factors being the major causes. We investigated the relationships between synoptic atmospheric patterns (i.e. weather types, WTs) and runoff, erosion and sediment yield throughout the Mediterranean basin by analyzing a large database of natural rainfall events at 68 research sites in 9 countries. Principal Component Analysis (PCA) was used to identify spatial relationships of the different WTs including three hydro-sedimentary variables: rainfall, runoff, and sediment yield (SY, used to refer to both soil erosion measured at plot scale and sediment yield registered at catchment scale). The results indicated 4 spatial classes of rainfall and runoff: (a) northern sites dependent on North (N) and North West (NW) flows; (b) eastern sites dependent on E and NE flows; (c) southern sites dependent on S and SE flows; and, finally, (d) western sites dependent on W and SW flows. Conversely, three spatial classes are identified for SY characterized by: (a) N and NE flows in northern sites (b) E flows in eastern sites, and (c) W and SW flows in western sites. Most of the rainfall, runoff and SY occurred during a small number of daily events, and just a few WTs accounted for large percentages of the total. Our results confirm that characterization by WT improves understanding of the general conditions under which runoff and SY occur, and provides useful information for understanding the spatial variability of runoff, and SY throughout the Mediterranean basin. The approach used here could be useful to aid of the design of regional water management and soil conservation measures
Spatial variability of the relationships of runoff and sediment yield with weather types throughout the Mediterranean basin
Soil degradation by water is a serious environmental problem worldwide, with specific climatic factors being the major causes. We investigated the relationships between synoptic atmospheric patterns (i.e. weather types, WI's) and runoff, erosion and sediment yield throughout the Mediterranean basin by analyzing a large database of natural rainfall events at 68 research sites in 9 countries. Principal Component Analysis (PCA) was used to identify spatial relationships of the different WTs including three hydro-sedimentary variables: rainfall, runoff, and sediment yield (SY, used to refer to both soil erosion measured at plot scale and sediment yield registered at catchment scale). The results indicated 4 spatial classes of rainfall and runoff: (a) northern sites dependent on North (N) and North West (NW) flows; (b) eastern sites dependent on E and NE flows; (c) southern sites dependent on S and SE flows; and, finally, (d) western sites dependent on W and SW flows. Conversely, three spatial classes are identified for SY characterized by: (a) N and NE flows in northern sites (b) E flows in eastern sites, and (c) W and SW flows in western sites. Most of the rainfall, runoff and SY occurred during a small number of daily events, and just a few WTs accounted for large percentages of the total. Our results confirm that characterization by WT improves understanding of the general conditions under which runoff and SY occur, and provides useful information for understanding the spatial variability of runoff, and SY throughout the Mediterranean basin. The approach used here could be useful to aid of the design of regional water management and soil conservation measures