PM2.5‑induced liver injury mediated by lipid accumulation via the endoplasmic reticulum stress-related IRE1α‑XBP1s pathway in mice.

Abstract

Atmospheric fine particulate matter (PM2.5) is a common atmospheric pollutant which presents substantial risk to human life. Numerous epidemiological and animal studies demonstrated a correlation between PM2.5 exposure and hepatic steatosis, as well as liver injury, increasing the incidence of related diseases, so the underlying molecular mechanism is worthy of further exploration. In this study, after 12 weeks of PM2.5 exposure in mice, liver histopathological examination and assessment of liver injury demonstrated that PM2.5-induced lipid accumulation primarily stems from synthesis of triglyceride (TG). It was found that the differentially expressed proteins in liver between PM2.5- and control- mice were closely related to the processing of endoplasmic reticulum and fatty acid metabolism by proteomics. Therefore, the study verified the protein expression of IRE1α-XBP1s pathway, which is most related to lipid synthesis during endoplasmic reticulum processing, increased as the PM2.5 concentration elevated. Further, when a specific inhibitor of IRE1α-XBP1s pathway was administered on mice while they were exposed to PM2.5, it was found that the inhibitor not only down-regulated the protein expression of this pathway, but also alleviated the lipid accumulation and liver injury induced by PM2.5. These findings confirmed that PM2.5 over-activated TG synthesis through the endoplasmic reticulum stress IRE1α-XBP1s signaling pathway, resulting in lipid accumulation and liver injury. Hence, this study could provide a targeted therapeutic site for the prevention and treatment of liver lipid metabolism disorders caused by air pollution.

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