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...

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Published inInternational journal of molecular sciences Vol. 23; no. 10; p. 5342
Main Authors Tang, Yanping, Fan, Yanan, Luo, Qing, Song, Guanbin
Format Journal Article
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
Author Fan, Yanan
Song, Guanbin
Tang, Yanping
Luo, Qing
AuthorAffiliation College of Bioengineering, Chongqing University, Chongqing 400030, China; 201919021048@cqu.edu.cn (Y.T.); fanyanan@cqu.edu.cn (Y.F.); qing.luo@cqu.edu.cn (Q.L.)
AuthorAffiliation_xml – name: College of Bioengineering, Chongqing University, Chongqing 400030, China; 201919021048@cqu.edu.cn (Y.T.); fanyanan@cqu.edu.cn (Y.F.); qing.luo@cqu.edu.cn (Q.L.)
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CitedBy_id crossref_primary_10_1016_j_hermed_2023_100731
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Keywords ERK1/2–Dicer signal
hepatocyte
DNA damage
compressive stress
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Snippet Alteration of liver tissue mechanical microenvironment is proven to be a key factor for causing hepatocyte injury and even triggering the occurrence of...
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SubjectTerms 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
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Title Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2-Dicer Signaling Pathway
URI https://www.ncbi.nlm.nih.gov/pubmed/35628153
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Volume 23
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