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Published on: April 30, 2020
Wnt Ligands Differentially Regulate Toxicity and Translocation of Graphene Oxide through Different Mechanisms in
Lingtong Zhi1, Mingxia Ren1, Man Qu1
1Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
Abstract:
In this study, we investigated the possible involvement of Wnt signals in the control of graphene oxide (GO) toxicity using the in vivo assay system of Caenorhabditis elegans. In nematodes, the Wnt ligands, CWN-1, CWN-2, and LIN-44, were found to be involved in the control of GO toxicity. Mutation of cwn-1 or lin-44 gene induced a resistant property to GO toxicity and resulted in the decreased accumulation of GO in the body of nematodes, whereas mutation of cwn-2 gene induces a susceptible property to GO toxicity and an enhanced accumulation of GO in the body of nematodes. Genetic interaction assays demonstrated that mutation of cwn-1 or lin-44 was able to suppress the susceptibility to GO toxicity shown in the cwn-2 mutants. Loss-of-function mutations in all three of these Wnt ligand genes resulted in the resistance of nematodes to GO toxicity. Moreover, the Wnt ligands might differentially regulate the toxicity and translocation of GO through different mechanisms. These findings could be important in understanding the function of Wnt signals in the regulation of toxicity from environmental nanomaterials.
Insights
Wnt signals regulate graphene oxide (GO) toxicity in C. elegans. Mutations in Wnt ligand genes CWN-1, CWN-2, and LIN-44 altered GO accumulation and toxicity, revealing Wnt pathways
Area of Science:
- Environmental toxicology
- Developmental biology
- Nanomaterial safety
Background:
- Graphene oxide (GO) is a nanomaterial with potential environmental applications.
- Understanding the biological impact of GO, including its toxicity and translocation, is crucial.
- Wnt signaling pathways are fundamental in various biological processes, including development and cell communication.
Purpose of the Study:
- To investigate the role of Wnt signaling in controlling graphene oxide (GO) toxicity.
- To elucidate how specific Wnt ligands (CWN-1, CWN-2, LIN-44) influence GO accumulation and toxicity in vivo.
- To explore the mechanisms by which Wnt signals modulate nanomaterial toxicity.
Main Methods:
- Utilized the in vivo assay system of Caenorhabditis elegans (nematodes).
- Conducted genetic analysis involving mutations in Wnt ligand genes (cwn-1, cwn-2, lin-44).
- Performed genetic interaction assays to study the interplay between Wnt ligands in GO toxicity.
Main Results:
- Mutations in cwn-1 or lin-44 conferred resistance to GO toxicity and reduced GO accumulation.
- Mutation in cwn-2 led to increased susceptibility to GO toxicity and enhanced GO accumulation.
- Loss-of-function mutations in all three Wnt ligand genes resulted in overall resistance to GO toxicity.
- Genetic interactions showed that cwn-1 and lin-44 mutations could suppress cwn-2-induced susceptibility.
Conclusions:
- Wnt signaling pathways play a significant role in regulating graphene oxide toxicity and accumulation in C. elegans.
- Specific Wnt ligands differentially modulate GO toxicity and translocation through distinct mechanisms.
- These findings provide insights into the function of Wnt signals in nanomaterial toxicity, relevant for environmental and health safety assessments.
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