Results from omic approaches in rat or mouse models exposed to inhaled crystalline silica: a systematic review

Abstract

Background: Crystalline silica (cSiO₂) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO₂ through inhalation. cSiO₂ inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO₂ microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO₂ effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO₂ in mice and rats and to highlight key results from omic data in rodents also validated in human.

Methods: The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO₂ and utilized omic approaches to identify pathways modulated by cSiO₂. Data were extracted and quality assessment was based on the SYRCLE's Risk of Bias tool for animal studies.

Results: Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO₂ exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans.

Conclusion: Omic technics offer new insights on the effects of cSiO₂ exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO₂ need to be further studied to better understand cSiO₂-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO₂ exposure.

Keywords: Autoimmunity; Crystalline silica; Environmental exposure; Mice; Omics; Rat.