Profiling Transcriptional Regulation and Functional Roles of Schistosoma mansoni c-Jun N-Terminal Kinase

Abstract

Mitogen-activated protein kinases (MAPKs) play a regulatory role and influence various biological activities, such as cell proliferation, differentiation, and survival. Our group has demonstrated through functional studies that Schistosoma mansoni c-Jun N-terminal kinase (SmJNK) MAPK is involved in the parasite’s development, reproduction, and survival. SmJNK can, therefore, be considered a potential target for the development of new drugs. Considering the importance of SmJNK in S. mansoni maturation, we aimed at understanding of SmJNK regulated signaling pathways in the parasite, correlating expression data with S. mansoni development. To better understand the role of SmJNK in S. mansoni intravertebrate host life stages, RNA interference knockdown was performed in adult worms and in schistosomula larval stage. SmJNK knocked-down in adult worms showed a decrease in oviposition and no significant alteration in their movement. RNASeq libraries of SmJNK knockdown schistosomula were sequenced. A total of 495 differentially expressed genes were observed in the SmJNK knockdown parasites, of which 373 were down-regulated and 122 up-regulated. Among the down-regulated genes, we found transcripts related to protein folding, purine nucleotide metabolism, the structural composition of ribosomes and cytoskeleton. Genes coding for proteins that bind to nucleic acids and proteins involved in the phagosome and spliceosome pathways were enriched. Additionally, we found that SmJNK and Smp38 MAPK signaling pathways converge regulating the expression of a large set of genes. C. elegans orthologous genes were enriched for genes related to sterility and oocyte maturation, corroborating the observed phenotype alteration. This work allowed an in-depth analysis of the SmJNK signaling pathway, elucidating gene targets of regulation and functional roles of this critical kinase for parasite maturation.

Toxocara canis Differentially Affects Hepatic MicroRNA Expression in Beagle Dogs at Different Stages of Infection

“…The MAPK signaling pathway participated in diverse cellular responses, such as inflammation, differentiation, proliferation, and apoptosis (43). Additionally, the MAPK signaling pathway is involved in the development, reproduction, and survival of Schistosoma mansoni (44). The Fc epsilon RI is the primary receptor in mast cells, which can influence the synthesis of proinflammatory cytokines and other molecules that are involved in inflammatory responses (45) (Figure 4A).…”

Transcriptomic changes in bovine skeletal muscle cells after resveratrol treatment

“…The tissue development GO term was also found in the enrichment analysis for the gilthead seabream when compared to all seabream 454 sequences to the novel EST sequences (Yúfera et al, 2012) and fibroblasts in the scarred rat (Kishimoto et al, 2016). In addition, the drug binding (GO:0008144) in this study (Supplementary file 2) is the significant GO term in schistosomula mansoni after c-Jun N-terminal kinase knockdown where the downregulated DEGs were enriched (Gava et al, 2019). Also, PI3K-AKT signaling pathway (bta04151) (Supplementary file 2) plays a key role in the dynamic switch between distinct KSRP functions which is favorable for skeletal myogenesis (Briata et al, 2012), while reducing the activities of this pathway in skeletal muscle could result in intrauterine growth restriction (Xing et al, 2019).…”

Docking-Based Virtual Screening Enables Prioritizing Protein Kinase Inhibitors With In Vitro Phenotypic Activity Against Schistosoma mansoni

“…We hypothesized that a drug able to target multiple kinases, especially those that participate in overlapping signaling cascades (e.g., MAP kinases), would be beneficial in terms of inhibition of a redundant signaling pathway. Indeed, RNAi knockdown of several MAP kinase proteins has shown to consistently affect S. mansoni development and/or reproduction (Andrade et al, 2014;Avelar et al, 2019;Tavares et al, 2020) and also regulate many genes in common (Gava et al, 2019). Here, we reported 91 compounds predicted to target the five analyzed target kinases, from which 14 and 27 presented activity against schistosomula and adult worms, respectively.…”