Review: Schistosoma mansoni phosphatidylinositol 3 kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway

Abou-El-Naga, Iman F.

doi:10.1016/j.cbpb.2021.110632

Cited by 4 publications

(3 citation statements)

References 82 publications

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“…A study has reported that the PI3K/Akt/mTOR signal has a critical role in the biology of S. mansoni ; it is involved in glucose uptake by S. mansoni , the reproduction of S. mansoni , and worm survival [ 30 ]. However, whether the Akt/mTOR pathway can impact on liver immunopathology caused by S. japonicum infection through regulating macrophage autophagy has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Galectin-receptor interaction: a key player in liver fibrosis induced by Schistosoma japonicum infection

Huang,

Liu,

Huang

et al. 2024

Parasites Vectors

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Background Schistosoma japonicum eggs lodge in the liver and induce a fibrotic granulomatous immune response in the liver of host. Galectin 3 (Gal-3) is a protein implicated in fibrosis in multiple organs. However, the pathology and molecular mechanisms promoting hepatic granuloma formation remain poorly understood. Methods To investigate the effect of blocking galectin-receptor interactions by α-lactose on liver immunopathology in mice with S. japonicum infection, C57BL/6 mice were infected with S. japonicum and alpha (α)-lactose was intraperitoneally injected to block the interactions of galectins and their receptors. Results Compared with S. japonicum-infected mice, there were significantly decreased Gal-3 mRNA and protein expression levels, decreased intensity of Gal-3 fluorescence in the liver, decreased serum ALT and AST levels, decreased egg numbers of S. japonicum in the liver section, attenuated hepatic and spleen pathology, and alleviated liver fibrosis accompanied with decreased protein expression levels of fibrosis markers [α-smooth muscle actin (α-SMA), collagen I, and collagen IV] in the liver of S. japonicum-infected mice blocked galectin-receptor interactions with hematoxylin-eosin staining, Masson’s trichrome staining, immunohistochemistry, or Western blot analysis. Compared with S. japonicum-infected mice, blocking galectin-receptor interactions led to increased eosinophil infiltration and higher eosinophil cationic protein (ECP) expression in the liver, accompanied by increased mRNA levels of eosinophil granule proteins [ECP and eosinophil peroxidase (EPO)], IL-5, CCL11, and CCR3 in the liver and decreased mRNA levels of Gal-3 and M2 macrophage cytokines (TGF-β, IL-10, and IL-4) in the liver and spleen by using quantitative real-time reverse transcription-polymerase chain reaction. In addition, there were increased Beclin1 protein expression and protein expression ratio of LC3B-II/LC3B-I and decreased p62 protein expression and protein expression ratios of phospho-mTOR/mTOR and phospho-AKT/AKT by Western blot; increased double-labeled F4/80+/LC3B+ cells by immunofluorescence staining; increased M1 macrophage polarization in the liver of S. japonicum-infected mice blocked galectin-receptor interactions by flow cytometric analysis and immunofluorescence staining. Conclusions Our data found that blockage of galectin-receptor interactions downregulated Gal-3, which in turn led to reduced liver functional damage, elevated liver eosinophil recruitment, promoted macrophage autophagy through the Akt/mTOR signaling pathway, and alleviated liver pathology and fibrosis. Therefore, Gal-3 plays a pivotal role during S. japonicum infection and could be a target of pharmacologic potential for liver fibrosis induced by S. japonicum infection. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Galectin-receptor interaction: a key player in liver fibrosis induced by Schistosoma japonicum infection

Huang,

Liu,

Huang

et al. 2024

Parasites Vectors

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“…They also revealed that mature eggs with 124 proteins differential to immature eggs are more likely to stimulate host immune responses [ 41 ]. Currently, our findings have identified the heat shock protein [ 51 ], phosphorylation-associated enzymes or kinases [ 52 , 53 ], Sm16 [ 54 ], GSTA3 [ 55 ], MMP7 [ 56 ], GPCRs [ 57 ], EF1-α [ 58 ], and other protein components that have been associated with schistosome-induced liver fibrosis. Many studies have confirmed that proteins related to fibrosis and inflammation are closely related to type II immune responses.…”

Section: Discussionmentioning

confidence: 99%

Differential Analysis of Key Proteins Related to Fibrosis and Inflammation in Soluble Egg Antigen of Schistosoma mansoni at Different Infection Times

Chen

Peng

et al. 2023

Pathogens

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Schistosomiasis is a major global health problem. Schistosomes secrete antigens into the host tissue that bind to chemokines or inhibit immune cell receptors, regulating the immune responses to allow schistosome development. However, the detailed mechanism of chronic schistosome infection-induced liver fibrosis, including the relationship between secreted soluble egg antigen (SEA) and hepatic stellate cell (HSC) activation, is still unknown. We used mass spectrometry to identify the SEA protein sequences from different infection weeks. In the 10th and 12th infection weeks, we focused on the SEA components and screened out the special protein components, particularly fibrosis- and inflammation-related protein sequences. Our results have identified heat shock proteins, phosphorylation-associated enzymes, or kinases, such as Sm16, GSTA3, GPCRs, EF1-α, MMP7, and other proteins linked to schistosome-induced liver fibrosis. After sorting, we found many special proteins related to fibrosis and inflammation, but studies proving their association with schistosomiasis infection are limited. Follow-up studies on MICOS, MATE1, 14-3-3 epsilon, and CDCP1 are needed. We treated the LX-2 cells with the SEA from the 8th, 10th, and 12th infection weeks to test HSC activation. In a trans-well cell model in which PBMCs and HSCs were co-cultured, the SEA could significantly induce TGF-β secretion, especially from the 12th week of infection. Our data also showed that TGF-β secreted by PBMC after the SEA treatment activates LX-2 and upregulates hepatic fibrotic markers α-SMA and collagen 1. Based on these results, the CUB domain-containing protein 1 (CDCP1) screened at the 12th infection week could be investigated further. This study clarifies the trend of immune mechanism variation in the different stages of schistosome infection. However, how egg-induced immune response transformation causes liver tissue fibrosis needs to be studied further.

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“…The PI3K-AKT is a core signaling pathway regulating cellular functions such as growth, proliferation, migration, and survival [ 82 , 83 ]. It plays a significant role in antioxidant reactions [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Preliminary study on toxicological mechanism of golden cuttlefish (Sepia esculenta) larvae exposed to cd

Liu,

Bao,

Yang

et al. 2023

BMC Genomics

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Background Cadmium (Cd) flows into the ocean with industrial and agricultural pollution and significantly affects the growth and development of economic cephalopods such as Sepia esculenta, Amphioctopus fangsiao, and Loligo japonica. As of now, the reasons why Cd affects the growth and development of S. esculenta are not yet clear. Results In this study, transcriptome and four oxidation and toxicity indicators are used to analyze the toxicological mechanism of Cd-exposed S. esculenta larvae. Indicator results indicate that Cd induces oxidative stress and metal toxicity. Functional enrichment analysis results suggest that larval ion transport, cell adhesion, and some digestion and absorption processes are inhibited, and the cell function is damaged. Comprehensive analysis of protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore S. esculenta larval toxicological mechanisms, and we find that among the 20 identified key genes, 14 genes are associated with neurotoxicity. Most of them are down-regulated and enriched to the neuroactive ligand-receptor interaction signaling pathway, suggesting that larval nervous system might be destroyed, and the growth, development, and movement process are significantly affected after Cd exposure. Conclusions S. esculenta larvae suffered severe oxidative damage after Cd exposure, which may inhibit digestion and absorption functions, and disrupt the stability of the nervous system. Our results lay a function for understanding larval toxicological mechanisms exposed to heavy metals, promoting the development of invertebrate environmental toxicology, and providing theoretical support for S. esculenta artificial culture.

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Review: Schistosoma mansoni phosphatidylinositol 3 kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway

Cited by 4 publications

References 82 publications

Galectin-receptor interaction: a key player in liver fibrosis induced by Schistosoma japonicum infection

Galectin-receptor interaction: a key player in liver fibrosis induced by Schistosoma japonicum infection

Differential Analysis of Key Proteins Related to Fibrosis and Inflammation in Soluble Egg Antigen of Schistosoma mansoni at Different Infection Times

Preliminary study on toxicological mechanism of golden cuttlefish (Sepia esculenta) larvae exposed to cd

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