ABSTRACT
The clinical application of doxorubicin (DOX) is limited because of its cardiotoxicity. However, the pathogenic mechanism of DOX and the role of miRNA in DOX-induced cardiotoxicity remain to be further studied. This study aimed to investigate the role of miR-199 in DOX-mediated cardiotoxicity. A mouse model of myocardial cell injury induced by DOX was established. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression changes of miR-199 and TATA-binding protein associated factor 9B (TAF9b) in DOX-induced cardiac injury. Cell apoptosis was detected by TUNEL staining and flow cytometry. The expression levels of apoptosis-related proteins, namely, Bax and Bcl-2, were detected by qPCR. The expression of Beclin-1 and LC3b was detected by western blotting. The binding effect of miR-199 with TAF9b was verified by dual-luciferase reporter gene assay. In this study, overexpression of miR-199 could promote cardiotoxicity. Inhibition of miR-199 could alleviate DOX-mediated myocardial injury. Further studies showed that miR-199 targeted TAF9b. Moreover, miR-199 promoted apoptosis of myocardial cells and aggravated autophagy. Furthermore, we demonstrated that TAF9B knockdown reversed the myocardial protective effect of miR-199 inhibitors. Therefore, miR-199 promoted DOX-mediated cardiotoxicity by targeting TAF9b, thereby aggravating apoptosis and regulating autophagy.
ABSTRACT
Light is perceived by photoreceptors in fungi and further integrated into the stress-activated MAPK HOG pathway, and thereby potentially activates the expression of genes for stress responses. This indicates that the precise control of light conditions can likely improve the conidial yield and stress resistance to guarantee the low cost and long shelf life of Trichoderma-based biocontrol agents and biofertilizers. In this study, effects of wavelengths and intensities of light on conidial yield and stress tolerance to osmotic, oxidative and pH stresses in Trichoderma guizhouense were investigated. We found that 2 µmol photons/(m2 × s) of blue light increased the conidial yield more than 1000 folds as compared to dark condition and simultaneously enhanced conidial stress resistance. The enhanced conidial stress resistance is probably due to the upregulated stress-related genes in blue light, which is under the control of the blue light receptor BLR1 and the MAP kinase HOG1.
ABSTRACT
Conidia of Trichoderma guizhouense (Hypocreales, Ascomycota) are frequently applied to the production of biofertilizers and biocontrol agents. Conidiation of some Trichoderma species depends on blue light and the action of different blue light receptors. However, the interplay between different blue-light receptors in light signalling remained elusive. Here, we studied the functions of the blue light receptors BLR1 and ENV1, and the MAP kinase HOG1 in blue light signalling in T. guizhouense. We found that the BLR1 dominates light responses and ENV1 is responsible for photoadaptation. Genome-wide gene expression analyses revealed that 1615 genes, accounting for ~13.4% of the genes annotated in the genome, are blue-light regulated in T. guizhouense, and remarkably, these differentially expressed genes (DEGs) including 61 transcription factors. BLR1 and HOG1 are the core components of the light signalling network, which control 79.9% and 73.9% of the DEGs respectively. In addition, the strict regulation of hydrophobin production by the blue light signalling network is impressive. Our study unravels the regulatory network based on the blue light receptors and the MAPK HOG pathway for conidiation, hydrophobin production and other processes in T. guizhouense.
