Developmental basis for intestinal barrier against the toxicity of graphene oxide

Background: Intestinal barrier is crucial for animals against translocation of engineered nanomaterials (ENMs) into secondary targeted organs. However, the molecular mechanisms for the role of intestinal barrier against ENMs toxicity are still largely unclear. The intestine of Caenorhabditis elegans is a powerful in vivo experimental system for the study on intestinal function. In this study, we investigated the molecular basis for intestinal barrier against toxicity and translocation of graphene oxide (GO) using C elegans as a model animal. Results: Based on the genetic screen of genes required for the control of intestinal development at different aspects using intestine-specific RNA interference (RNAi) technique, we identified four genes (erm-1, pkc-3, hmp-2 and act-5) required for the function of intestinal barrier against GO toxicity. Under normal conditions, mutation of any of these genes altered the intestinal permeability. With the focus on PKC-3, an atypical protein kinase C, we identified an intestinal signaling cascade of PKC-3-SEC-8-WTS-1, which implies that PKC-3 might regulate intestinal permeability and GO toxicity by affecting the function of SEC-8-mediated exocyst complex and the role of WTS-1 in maintaining integrity of apical intestinal membrane. ISP-1 and SOD-3, two proteins required for the control of oxidative stress, were also identified as downstream targets for PKC-3, and functioned in parallel with WTS-1 in the regulation of GO toxicity. Conclusions: Using C elegans as an in vivo assay system, we found that several developmental genes required for the control of intestinal development regulated both the intestinal permeability and the GO toxicity. With the focus on PKC 3, we raised two intestinal signaling cascades, PKC-3-SEC-8-VVTS-1 and PKC-3-ISP-1/SOD-3. Our results will strengthen our understanding the molecular basis for developmental machinery of intestinal barrier against GO toxicity and translocation in animals.