The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells
PHYTOTHERAPY RESEARCH
Authors: Ji, Tao; Su, Shu-lan; Zhu, Yue; Guo, Jian-ming; Qian, Da-wei; Tang, Yu-ping; Duan, Jin-ao
Abstract
Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.
The fungal NADPH oxidase is an essential element for the molecular dialog between Trichoderma and Arabidopsis
PLANT JOURNAL
Authors: Villalobos-Escobedo, Jose M.; Esparza-Reynoso, Sarai; Pelagio-Flores, Ramon; Lopez-Ramirez, Fabiola; Ruiz-Herrera, Leon F.; Lopez-Bucio, Jose; Herrera-Estrella, Alfredo
Abstract
Members of the fungal genus Trichoderma stimulate growth and reinforce plant immunity. Nevertheless, how fungal signaling elements mediate the establishment of a successful Trichoderma-plant interaction is largely unknown. In this work, we analyzed growth, root architecture and defense in an Arabidopsis-Trichoderma co-cultivation system, including the wild-type (WT) strain of the fungus and mutants affected in NADPH oxidase. Global gene expression profiles were assessed in both the plant and the fungus during the establishment of the interaction.Trichoderma atrovirideWT improved root branching and growth of seedling as previously reported. This effect diminished in co-cultivation with the increment nox1, increment nox2and increment noxRnull mutants. The data gathered of the Arabidopsis interaction with the increment noxRstrain showed that the seedlings had a heightened immune response linked to jasmonic acid in roots and shoots. In the fungus, we observed repression of genes involved in complex carbohydrate degradation in the presence of the plant before contact. However, in the absence of NoxR, such repression was lost, apparently due to a poor ability to adequately utilize simple carbon sources such as sucrose, a typical plant exudate. Our results unveiled the critical role played by the Trichoderma NoxR in the establishment of a fine-tuned communication between the plant and the fungus even before physical contact. In this dialog, the fungus appears to respond to the plant by adjusting its metabolism, while in the plant, fungal perception determines a delicate growth-defense balance.