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

• Published in: International journal of molecular sciences Vol. 23; no. 10; p. 5342
• Main Authors: Tang, Yanping, Fan, Yanan, Luo, Qing, Song, Guanbin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.05.2022; MDPI
• Subjects: Apoptosis; Cell cycle; Compressive properties; compressive stress; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; ERK1/2–Dicer signal; Extracellular signal-regulated kinase; Gene expression; Hepatocellular carcinoma; hepatocyte; Hepatocytes; Kinases; Liver; Liver cancer; Liver diseases; Microenvironments; Mutation; Phosphorylation; Pressure; Pressure effects; Proteins; Signal transduction; Stem cells; ERK1/2–Dicer signal; hepatocyte; DNA damage; compressive stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23105342

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.