Regulation of Schistosoma mansoni Development and Reproduction by the Mitogen-Activated Protein Kinase Signaling Pathway

Abstract

BackgroundProtein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear.Methodology/Principal FindingsWe employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade.ConclusionsWe conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.

LncRNA‐TCONS_00026907 is involved in the progression and prognosis of cervical cancer through inhibiting miR‐143‐5p

“…A quantity of 1 μ g of total RNA was reversely transcribed with random primers, using the RevertAid First Strand cDNA Synthesis kit (Thermo Fisher Scientific, USA). As described previously , the SYBR‐Green PCR Master Mix kit (Takara, Japan) was used to measure the mRNA expression levels of TCONS_00026907, miR‐143‐5p, and ELK1. The primer sequences for GAPDH (internal control) are 5′‐CCT CGT CTC ATA GAC AAG ATG GT‐3′ (forward primer) and 5′‐GGG TAG AGT CAT ACT GGA ACA TG‐3′ (reverse primer).…”

Comprehensive phenotyping and transcriptome profiling to study nanotoxicity inC. elegans

“…Ribosome, proteasome, aminoacyl-tRNA biosynthesis and RNA transport were significantly upregulated in both groups, indicating overall higher rate of protein turnover upon exposure. In contrast, biological pathways reflecting phenotypes including neuroactive ligand-receptor interaction [regulating locomotion (Kong et al, 2015)], wnt-signaling (regulating reproduction and cell growth (Inoki et al, 2006;Hernandez Gifford, 2015) and MAPK signaling (regulating reproduction and cell growth (Zhang & Liu, 2002;Andrade et al, 2014) were significantly down-regulated in both exposures (Fig. 7).…”

“…The top 20 significant KEGG pathways identified in both exposure studies are similar to the findings based on GO BPs. In particular, the regulatory biological pathways linked to phenotypes, including neuroactive ligand-receptor interaction (relates to locomotion Inoki et al, 2016), wnt and MAPK signaling pathways (relates to reproduction and cell growth (Inoki et al, 2016;Hernandez Gifford, 2015;Zhang & Liu, 2002;Andrade et al, 2014)), were found to be downregulated in both experiments. The pathway interaction analysis by ClueGO showed that wnt signaling pathway was interacting with tgf-beta pathway which was also enriched with significantly negative NES in both toxicities.…”

SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced granuloma development

“…Robust activation of the ERK1/2, p38 pathways, as well as the JNK MAPK pathway was observed in SjE16.7 stimulated macrophages. Previous work has shown that schistosome egg antigens stimulate MAPK pathways in macrophages, dendritic cells and trophoblast cells (Wang et al, 2006;Andrade et al, 2014;Ressurreicao et al, 2011), and since SjE16.7 is a protein component of schistosome eggs it is perhaps not surprising that SjE16.7 also induces MAPK activation in macrophages. RacGTPases are small signaling G proteins implicated in the control of cytoskeletal events as well as in coordinating diverse cellular functions (Bustelo et al, 2007;Pai et al, 2010).…”