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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140865/ https://www.ncbi.nlm.nih.gov/pubmed/35628153 http://dx.doi.org/10.3390/ijms23105342 |
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author | Tang, Yanping Fan, Yanan Luo, Qing Song, Guanbin |
author_facet | Tang, Yanping Fan, Yanan Luo, Qing Song, Guanbin |
author_sort | Tang, Yanping |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9140865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91408652022-05-28 Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2–Dicer Signaling Pathway Tang, Yanping Fan, Yanan Luo, Qing Song, Guanbin Int J Mol Sci Article 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. MDPI 2022-05-10 /pmc/articles/PMC9140865/ /pubmed/35628153 http://dx.doi.org/10.3390/ijms23105342 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tang, Yanping Fan, Yanan Luo, Qing Song, Guanbin Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2–Dicer Signaling Pathway |
title | Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2–Dicer Signaling Pathway |
title_full | Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2–Dicer Signaling Pathway |
title_fullStr | Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2–Dicer Signaling Pathway |
title_full_unstemmed | Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2–Dicer Signaling Pathway |
title_short | Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2–Dicer Signaling Pathway |
title_sort | pressure loading induces dna damage in human hepatocyte line l02 cells via the erk1/2–dicer signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140865/ https://www.ncbi.nlm.nih.gov/pubmed/35628153 http://dx.doi.org/10.3390/ijms23105342 |
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