Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2-Dicer Signaling Pathway

Alteration of liver tissue mechanical microenvironment is proven to be a key factor for causing hepatocyte injury and even triggering the occurrence of hepatocellular carcinoma; however, the underlying mechanisms involved are not fully understood. In this study, using a customized, pressure-loading device, we assess the effect of pressure loading on DNA damage in human hepatocytes. We show that pressure loading leads to DNA damage and S-phase arresting in the cell cycle, and activates the DNA damage response in hepatocytes. Meanwhile, pressure loading upregulates Dicer expression, and its silencing exacerbates pressure-induced DNA damage. Moreover, pressure loading also activates ERK1/2 signaling molecules. Blockage of ERK1/2 signaling inhibits pressure-upregulated Dicer expression and exacerbates DNA damage by suppressing DNA damage response in hepatocytes. Our findings demonstrate that compressive stress loading induces hepatocyte DNA damage through the ERK1/2-Dicer signaling pathway, which provides evidence for a better understanding of the link between the altered mechanical environment and liver diseases.

Automated summary

In this study, we investigated the effect of pressure loading on human hepatocytes and found that it leads to DNA damage, cell cycle arrest, and activation of the DNA damage response. We also discovered that pressure loading upregulates Dicer expression and activates the ERK1/2 signaling pathway. Our findings suggest that compressive stress loading induces hepatocyte DNA damage through the ERK1/2-Dicer signaling pathway, providing evidence for a better understanding of the link between altered mechanical environment and liver diseases.