Tumour necrosis factor superfamily member 15 (Tnfsf15) facilitates lymphangiogenesis via up-regulation of Vegfr3 gene expression in lymphatic endothelial cells.

Lymphangiogenesis is essential in embryonic development but is rare in adults. It occurs, however, in many disease conditions including cancers. Vascular endothelial growth factor-C/D (VEGF-C/D) and VEGF receptor-3 (Vegfr3) play a critical role in the regulation of lymphangiogenesis. We investigated how the VEGF-C/Vegfr3 signalling system is regulated by tumour necrosis factor superfamily member 15 (Tnfsf15), an endothelium-derived cytokine. We report here that Tnfsf15, which is known to induce apoptosis in vascular endothelial cells, can promote lymphatic endothelial cell (LEC) growth and migration, stimulate lymphangiogenesis, and facilitate lymphatic circulation. Treatment of mouse LECs with Tnfsf15 results in up-regulation of Vegfr3 expression; this can be inhibited by gene silencing of death domain-containing receptor-3 (DR3; Tnfrsf25), a cell surface receptor for Tnfsf15, with siRNA, or by blocking Tnfsf15-DR3 interaction with a Tnfsf15 neutralizing antibody, 4-3H. Additionally, Tnfsf15/DR3 signalling pathways in LECs include activation of NF-κB. Tnfsf15-overexpressing transgenic mice exhibit a marked enhancement of lymph drainage; this is confirmed by treatment of wild-type mice with intraperitoneal injection of recombinant Tnfsf15. Moreover, systemic treatment of pregnant Tnfsf15 transgenic mice with 4-3H leads to inhibition of embryonic lymphangiogenesis. Our data indicate that Tnfsf15, a cytokine produced largely by endothelial cells, facilitates lymphangiogenesis by up-regulating Vegfr3 gene expression in LECs, contributing to the maintenance of the homeostasis of the circulatory system. This finding also suggests that Tnfsf15 may be of potential value as a therapeutic tool for the treatment of lymphoedema.

Dynamic change of vegetation and its response to climate and topographic factors in the Xijiang River basin, China.

Vegetation plays an important role in the energy exchange, water cycle, carbon cycle, biogeochemical cycle, and maintenance of surface ecosystems. In recent years, regional vegetation cover has changed significantly. This study used statistical analyses, including the Mann-Kendall trend test, the Hurst exponent, and Pettitt test, to analyze the characteristics of temporal and spatial variation of vegetation coverage in the Xijiang River basin from 2000 to 2013. The results showed that vegetation coverage of 98.76% of the Xijiang River basin is weakly variable (Cv < 0.1). The area with significantly increased vegetation accounts for 43.45% of the total area (p < = 0.05). A total of 19.47% of vegetation coverage in the Xijiang River basin had significant change-points from 2004 to 2008 (p < = 0.05), and the area of concave change-points accounted for 25.99% of the total area of point increased the vegetation coverage. At an altitude of 500-2000 m, the altitude has an inhibitory effect on vegetation coverage. When the slope is less than 35 degrees, the slope has a promoting effect on vegetation coverage. Rich precipitation resources are the main source of soil water supply, and higher temperature provides better thermal energy resources, which may have a significant impact on vegetation growth in the future and cause time lag effects of climatic factors on vegetation coverage. The vegetation coverage and the area affected by the precipitation and temperature (time lag factors) accounted for 32.99% and 31.47% of the total watershed, respectively. The correlation between climatic factors, topographic factors, and vegetation coverage increased over time. The results from this study will help to further deepen the understanding of vegetation cover and its influencing factors, and provide a scientific basis for ecological restoration projects such as vegetation restoration in the Xijiang River basin of China.

Growth, Morphological, and Physiological Responses to Drought Stress in Bothriochloa ischaemum.

Water shortage in the arid-semiarid regions of China seriously hampers ecosystem construction. Therefore, elucidation of the mechanisms by which vegetation in that area responds to drought stress may enable us to improve utilization of limited water resources and thus contend with the problem of drought and water shortage. We studied Bothriochloa ischaemum, a native grass species, conducted potting control tests to compare several indicators of B. ischaemum grown under three different moisture conditions (80%, 60%, 40% Field capacity represent sufficient water supply, mild water stress, and serious water stress, respectively). Plant response parameters measured included biomass accumulation, root morphology, transient water use efficiency (WUE), stable carbon isotope ratio (δ13C), and stable carbon isotope discrimination (Δ13C) of various plant organs and their interrelationships. B. ischaemum had the greatest WUE under mild drought stress. However, serious drought stress resulted in considerable decline in overall biomass but substantial increase in root-to-shoot ratio and fine-root biomass. Coarse-root biomass dropped appreciably, indicating that serious drought stress leads to allocation non-uniformity of the carbon "sink." δ13C and Δ13C of stem correlated considerably with root morphology, suggesting the feasibility of characterizing WUE, biomass, and root morphology of B. ischaemum via the stable carbon isotope approach. Our evaluation of 21 drought resistance indicators of B. ischaemum showed that under a given moisture treatment gradient one can isolate an optimal indicator to express growth, morphology, and physiology, to improve the accuracy of depicting plant drought resistance and simplify the drought resistance indicator system. This study elucidates the response mechanism of B. ischaemum to drought stress and provides theoretical support to screening of drought-resistant plants across the arid-semiarid regions of China.

Vascular endothelial growth factor suppresses TNFSF15 production in endothelial cells by stimulating miR-31 and miR-20a expression via activation of Akt and Erk signals.

Tumor necrosis factor superfamily-15 (TNFSF15; VEGI; TL1A) is a negative modulator of angiogenesis for blood vessel homeostasis and is produced by endothelial cells in a mature vasculature. It is known to be downregulated by vascular endothelial growth factor (VEGF), a major regulator of neovascularization but the mechanism of this interaction is unclear. Here we report that VEGF is able to stimulate the production of two microRNAs, miR-20a and miR-31, which directly target the 3'-UTR of TNFSF15. Additionally, we show that two VEGF-stimulated cell growth signals, Erk and Akt, are responsible for promoting the expression of miR-20a and miR-31. Treatment of human umbilical vein endothelial cells (HUVECs) with Akt inhibitor LY294002 results in diminished miR-20a and miR-31 production, while Erk inhibitor U0126 prevented VEGF-stimulated expression of miR-20a but not that of miR-31. Furthermore, inactivation of either Erk or Akt signals restores TNFSF15 gene expression. In an angiogenesis assay, elevated miR-20a or miR-31 levels in HUVECs leads to enhancement of capillary-like tubule formation in vitro, whereas lowered miR-20a and miR-31 levels results in an inhibition. These findings are consistent with the view that miR-20a and miR-31 mediate VEGF-induced downregulation of TNFSF15. Targeting these microRNA molecules may therefore provide an effective approach to inhibit angiogenesis.

[Response characteristics of soil water use patterns by different plants to precipitation in rocky mountainou areas.] / 土石山区不同植物土壤水分利用方式对降雨的响应特征.

Water-use characteristics of plants are important for vegetation restoration in shallow earth-rock mountain area. In this study, soil and plant samples of Platycladus orientalis and corn were collected after rainfall events in Yingwugou watershed of Dan River to analyze the signatures of oxygen isotopes and the response of water use patterns to precipitation using stable isotope technology. The results showed that there were different response characteristics of the soil water utilization to precipitation between P. orientalis and corn. The root of P. orientalis mainly used the soil moisture from 10-30 cm layer, while corn mainly used that in the depth of 0-20 cm. The water absorption depth (WAP) of P. orientalis root decreased from 20-30 cm to 10-20 cm, while that of corn altered from 10-20 cm to 0-20 cm, when precipitation decreased from 29 mm to 8 mm. The WAP of P. orientalis gradually changed from deep to shallow soil, while the main WAP of corn increased from 10-20 cm to 0-20 cm, whenprecipitation decreased. The response of P. orientalis and corn to precipitation was very obvious.

TNFSF15 suppresses VEGF production in endothelial cells by stimulating miR-29b expression via activation of JNK-GATA3 signals.

Vascular endothelial cell growth factor (VEGF) plays a pivotal role in promoting neovascularization. VEGF gene expression in vascular endothelial cells in normal tissues is maintained at low levels but becomes highly up-regulated in a variety of disease settings including cancers. Tumor necrosis factor superfamily 15 (TNFSF15; VEGI; TL1A) is an anti-angiogenic cytokine prominently produced by endothelial cells in a normal vasculature. We report here that VEGF production in mouse endothelial cell line bEnd.3 can be inhibited by TNFSF15 via microRNA-29b (miR-29b) that targets the 3'-UTR of VEGF transcript. Blocking TNFSF15 activity by using either siRNA against the TNFSF15 receptor known as death domain-containing receptor-3 (DR3; TNFRSF25), or a neutralizing antibody 4-3H against TNFSF15, led to inhibition of miR-29b expression and reinvigoration of VEGF production. In addition, we found that TNFSF15 activated the JNK signaling pathway as well as the transcription factor GATA3, resulting in enhanced miR-29b production. Treatment of the cells either with SP600125, an inhibitor of JNK, or with JNK siRNA, led to eradication of TNFSF15-induced GATA3 expression. Moreover, GATA3 siRNA suppressed TNFSF15-induced miR-29b expression. These findings suggest that VEGF gene expression can be suppressed by TNFSF15-stimulated activation of the JNK-GATA3 signaling pathway which gives rise to up-regulation of miR-29b.