N6-methyladenosine demethylase fat mass and obesity-associated protein suppresses hyperglycemia-induced endothelial cell injury by inhibiting reactive oxygen species formation via autophagy promotion.

INTRODUCTION: Hyperglycemia-induced endothelial cell injury is one of the main causes of diabetic vasculopathy. Fat mass and obesity-associated protein (FTO) was the first RNA N6-methyladenosine (m6A) demethylase identified; it participates in the pathogenesis of diabetes. However, the role of FTO in hyperglycemia-induced vascular endothelial cell injury remains unclear. MATERIALS AND METHODS: The effects of FTO on cellular m6A, autophagy, oxidative stress, proliferation, and cytotoxicity were explored in human umbilical vein endothelial cells (HUVECs) treated with high glucose (33.3 mmol/mL) after overexpression or pharmacological inhibition of FTO. MeRIP-qPCR and RNA stability assays were used to explore the molecular mechanisms by which FTO regulates autophagy. RESULTS: High glucose treatment increased m6A levels and reduced FTO protein expression in HUVECs. Wild-type overexpression of FTO markedly inhibited reactive oxygen species generation by promoting autophagy, increasing endothelial cell proliferation, and decreasing the cytotoxicity of high glucose concentrations. The pharmacological inhibition of FTO showed the opposite results. Mechanistically, we identified Unc-51-like kinase 1 (ULK1), a gene responsible for autophagosome formation, as a downstream target of FTO-mediated m6A modification. FTO overexpression demethylated ULK1 mRNA and inhibited its degradation in an m6A-YTHDF2-dependent manner, leading to autophagy activation. CONCLUSIONS: Our study demonstrates the functional importance of FTO-mediated m6A modification in alleviating endothelial cell injury under high glucose conditions and indicates that FTO may be a novel therapeutic target for diabetic vascular complications.

Cortistatin ameliorates Ang II-induced proliferation of vascular smooth muscle cells by inhibiting autophagy through SSTR3 and SSTR5.

AIMS: Vascular smooth muscle cell (VSMC) proliferation plays a significant role in the development of various vascular disorders. However, the effect of cortistatin (CST) on VSMC proliferation remains unclear. Therefore, the purpose of our research aimed to study whether CST protected VSMCs from angiotensin II (Ang II)-induced proliferation and which mechanisms participated in the process. MAIN METHODS: Cultured rat VSMCs were treated with Ang II with or without CST for 24 h. Cell proliferation rate was measured by cell counting kit-8 (CCK8) assay. The expressions of CST and its receptors were assessed by quantitative real-time PCR (qRT-PCR). The protein expression levels were analyzed by western blots. Immunofluorescence and transmission electron microscopy (TEM) were used to observe autophagy. KEY FINDINGS: Our results showed that different concentrations of CST alleviated the Ang II-induced VSMC proliferation. The autophagy and reactive oxygen species (ROS) stimulated by Ang II were attenuated by CST. Furthermore, when the autophagy inhibitor 3-methyladenine (3-MA) was added, it exerted similar inhibition effects like CST, but didn't augment the protective role of CST on Ang II-induced VSMC autophagy and proliferation. Moreover, blocking somatostatin receptor 3 and 5 (SSTR3 and SSTR5) partially abrogated the suppressive effect of CST on Ang II-stimulated VSMC proliferation and autophagy. SIGNIFICANCE: This study indicated that CST could ameliorate Ang II-stimulated VSMC proliferation by inhibiting autophagy partially through its receptors SSTR3 and SSTR5, providing a reasonable evidence for CST as a novel perspective therapeutic target of vascular diseases.

Bacterial Community Responses to Soils along a Latitudinal and Vegetation Gradient on the Loess Plateau, China.

Soil bacterial communities play an important role in nutrient recycling and storage in terrestrial ecosystems. Loess soils are one of the most important soil resources for maintaining the stability of vegetation ecosystems and are mainly distributed in northwest China. Estimating the distributions and affecting factors of soil bacterial communities associated with various types of vegetation will inform our understanding of the effect of vegetation restoration and climate change on these processes. In this study, we collected soil samples from 15 sites from north to south on the Loess Plateau of China that represent different ecosystem types and analyzed the distributions of soil bacterial communities by high-throughput 454 pyrosequencing. The results showed that the 142444 sequences were grouped into 36816 operational taxonomic units (OTUs) based on 97% similarity. The results of the analysis showed that the dominant taxonomic phyla observed in all samples were Actinobacteria, Proteobacteria, Chloroflexi, Acidobacteria and Planctomycetes. Actinobacteria and Proteobacteria were the two most abundant groups in all samples. The relative abundance of Actinobacteria increased from 14.73% to 40.22% as the ecosystem changed from forest to sandy, while the relative abundance of Proteobacteria decreased from 35.35% to 21.40%. Actinobacteria and Proteobacteria had significant correlations with mean annual precipitation (MAP), pH, and soil moisture and nutrients. MAP was significantly correlated with soil chemical and physical properties. The relative abundance of Actinobacteria, Proteobacteria and Planctomycetes correlated significantly with MAP, suggesting that MAP was a key factor that affected the soil bacterial community composition. However, along with the MAP gradient, Chloroflexi, Bacteroidetes and Cyanobacteria had narrow ranges that did not significantly vary with the soil and environmental factors. Overall, we conclude that the edaphic properties and/or vegetation types are driving bacterial community composition. MAP was a key factor that affects the composition of the soil bacteria on the Loess Plateau of China.

[Ecological stoichiometric characteristics in leaf and litter under different vegetation types of Zhifanggou watershed on the Loess Plateau, China].

The purpose was to characterize the effects of vegetation types on plant leaf and litter carbon (C), nitrogen (N), phosphorus (P), potassium (K) and C: N: P: K ecological stoichiometric characteristics in seven dominant plant species, including Robinia pseudoacacia, Syringa, Sophora viciifolia, Hippophae rhamnoides, Rosa xanthina, Artemisia sacrorum, Artemisia giraldii, of Zhifanggou Watershed on the Loess Plateau, China. This paper indicated the differences between the contents of C, N, P and K and the characteristics of ecological stoichiometric in the different vegetation types, including forest type, shrub type and grass type. Concentrations of C, N, P and K were measured, and C: N: P: K was estimated for different vegetation types. There were no significant differences in leaf C, N and P concentrations among the three vegetation types. But significant differences in leaf K concentration existed, and the K concentration in leaf was the highest in grass type, and the lowest in shrub type. The contents of C, N, P and K in leaf were much higher than those in litter, especially in shrub and grass types. The resorption efficiencies of C, N, P and K were different, and their ranges varied 6.16%-22.84%, 24.38%-65.18%, 22.38%-77.16% and 60.99%- 89.35%, respectively. Grass type had the highest C, P and K resorption efficiencies, and the lowest N resorption efficiency. Values of the N: P ratio in leaf varied in the range of 12.14-19.17, and varied in the range of 12.84-30.67 in litter. Values of the N: P ratio in leaf were the highest in shrub type (19. 17), and the lowest in grass (12. 14), indicating that the growth of shrub plants was limited by P, while the growth of grass plants was limited by N. The K concentration in leaf was significantly negatively correlated with values of the N: P ratio in leaf, and the K concentration in litter was significantly negatively correlated with values of the C: P ratio in leaf. Findings in this study highlighted the characteristics of accumulation and and return of leaf and litters nutrients during the different vegetation succession on the Loess Plateau.