Abstract
<title>Abstract</title> <p>Trichloroethylene (TCE) is a common industrial organic solvent. Exposure to TCE can induce occupational medicamentosa-like dermatitis (OMDT), which is frequently accompanied by liver and kidney injury. During the organ damage caused by TCE, mtDNA is a key molecule that mediates the interaction between the liver and the kidney. Our previous research has shown that mitochondrial DNA (mtDNA) released from hepatocytes damage under TCE sensitization can cause damage to renal tubular epithelial cells. However, the specific mechanism remains unclear. To this end, we established a TCE percutaneous sensitization mouse model. We found that in the TCE sensitization positive group, liver damage was strongly correlated with kidney damage. The Stimulator of Interferon Genes (STING) pathway in renal macrophages was activated, and the macrophages underwent M1 polarization accompanied by the formation of macrophage extracellular traps (METs). To further confirm the role of hepatocyte mtDNA, we extracted the mtDNA from the hepatocytes of TCE sensitization positive mice and injected it into normal mice. We found that the STING pathway in the kidney of the injection group was activated, and the macrophages also underwent M1 polarization. This phenomenon was significantly alleviated after intervention with the STING inhibitor C-176. We also confirmed this in vitro using RAW264.7 with hepatocyte mtDNA treatment. In summary, our work demonstrated that hepatocyte mtDNA can activate the STING pathway in renal macrophages, thereby causing M1 polarization of macrophages and the formation of METs. C-176 can alleviate this phenomenon.</p>