Rationale: Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic elastase inhibitors reverse experimental pulmonary hypertension but cause hepatotoxicity in clinical studies. The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary hypertension in mice, but its potential to improve endothelial function and BMPR2 signaling, and to reverse severe experimental pulmonary hypertension or vascular pathology in the human disease was unknown.Objectives: To assess elafin-mediated regression of pulmonary vascular pathology in rats and in lung explants from patients with pulmonary hypertension. To determine if elafin amplifies BMPR2 signaling in pulmonary artery endothelial cells and to elucidate the underlying mechanism.Methods: Rats with pulmonary hypertension induced by vascular endothelial growth factor receptor blockade and hypoxia (Sugen/ hypoxia) as well as lung organ cultures from patients with pulmonary hypertension were used to assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary arterial endothelial cells from patients and control subjects were used to determine the efficacy and mechanism of elafin-mediated BMPR2 signaling. Measurements and Main Results:In Sugen/hypoxia rats, elafin reduced elastase activity and reversed pulmonary hypertension, judged by regression of right ventricular systolic pressure and hypertrophy and pulmonary artery occlusive changes. Elafin improved endothelial function by increasing apelin, a BMPR2 target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells and decreased neointimal lesions in lung organ culture. In normal and patient pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically to augmented interaction of BMPR2 with caveolin-1 via elafin-mediated stabilization of endothelial surface caveolin-1.Conclusions: Elafin reverses obliterative changes in pulmonary arteries via elastase inhibition and caveolin-1-dependent amplification of BMPR2 signaling.

BackgroundRice (Oryza sativa L. ssp. indica) seeds as plant microbiome present both an opportunity and a challenge to colonizing bacterial community living in close association with plants. Nevertheless, the roles and activities of bacterial endophytes remain largely unexplored and insights into plant-microbe interaction are compounded by its complexity. In this study, putative functions or physiological properties associated with bacterial endophytic nature were assessed. Also, endophytic roles in plant growth and germination that may allow them to be selectively chosen by plants were also studied.ResultsThe cultivable seed endophytes were dominated by Proteobacteria particularly class Gammaproteobacteria. Highly identical type strains were isolated from the seed endosphere regardless of the rice host’s physiological tolerance to salinity. Among the type strains, Flavobacterium sp., Microbacterium sp. and Xanthomonas sp. were isolated from the salt-sensitive and salt-tolerant cultivars. PCA-Biplot ordination also showed that specific type strains isolated from different rice cultivars have distinguishing similar characteristics. Flavobacterium sp. strains are phosphate solubilizers and indole-3-acetic acid producers with high tolerance to salinity and osmotic stress. Pseudomonas strains are characterized as high siderophore producers while Microbacterium sp. and Xanthomonas sp. strains have very high pectinase and cellulase activity. Among the physiological traits of the seed endophytes, bacterial pectinase and cellulase activity are positively correlated as well as salt and osmotic tolerance. Overall characterization shows that majority of the isolates could survive in 4–8% salt concentration as well as in 0.6 M and 1.2 M sucrose solution. The activities of catalase, pectinase and cellulase were also observed in almost all of the isolates indicating the importance of these characteristics for survival and colonization into the seed endosphere. Seed bacterial endophytes also showed promising plant growth promoting activities including hormone modulation, nitrogen fixation, siderophore production and phosphate solubilization.ConclusionThough many of the isolates possess similar PGP and endophytic physiological traits, this study shows some prominent and distinguishing traits among bacterial groups indicating key determinants for their success as endophytes in the rice seed endosphere. Rice seeds are also inhabited by bacterial endophytes that promote growth during early seedling development.Electronic supplementary materialThe online version of this article (10.1186/s12866-017-1117-0) contains supplementary material, which is available to authorized users.

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Soil salinity, being a part of natural ecosystems, is an increasing problem in agricultural soils throughout the world. Pseudomonas frederiksbergensis OS261 has already been proved to be an effective bio-inoculant for enhancing cold stress tolerance in plants, however, its effect on salt stress tolerance is unknown. The main aim of the present study was to elucidate P. frederiksbergensis OS261 mediated salt stress tolerance in red pepper. The plants were exposed to a salt stress using NaCl at the concentrations of 50, 100, and 150 mM after 12 days of transplantation, while plant growth and enzyme activity were estimated 50 days after sowing. The height in P. frederiksbergensis OS261 inoculated plants was significantly increased by 19.05, 34.35, 57.25, and 61.07% compared to un-inoculated controls at 0, 50, 100, and 150 mM of NaCl concentrations, respectively, under greenhouse conditions. The dry biomass of the plants increased by 31.97, 37.47, 62.67, and 67.84% under 0, 50, 100, and 150 mM of NaCl concentrations, respectively. A high emission of ethylene was observed in un-inoculated red pepper plants under salinity stress. P. frederiksbergensis OS261 inoculation significantly reduced ethylene emission by 20.03, 18.01, and 20.07% at 50, 100, and 150 mM of NaCl concentrations, respectively. Furthermore, the activity of antioxidant enzymes (ascorbate peroxidase, superoxide dismutase, and catalase) also varied in the inoculated red pepper plants. Salt stress resistance in the bacterized plants was evident from the improved antioxidant activity in leaf tissues and the decreased hydrogen ion concentration. Thus, we conclude that P. frederiksbergensis OS261 possesses stress mitigating property which can enhance plant growth under high soil salinity by reducing the emission of ethylene and regulating antioxidant enzymes.

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