Extracellular vesicles activate ATM-Chk2 signaling pathway through the intercellular transfer of mitochondrial DNA in HBV-infected human hepatocytes

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatitis B virus (HBV) is a human hepatotropic pathogen causing hepatocellular carcinoma. We recently obtained HBV-susceptible immortalized human hepatocyte NKNT-3 by exogenously expressing NTCP and its derived cell clones, #28.3.8 and #28.3.25.13 exhibiting different levels of HBV susceptibility. In the present study, we showed that HBV infection activated the ATM-Chk2 signaling pathway in #28.3.25.13 cells but not in #28.3.8 cells. Both the cell culture supernatant and extracellular vesicles (EVs) derived from HBV-infected #28.3.25.13 cells also activated the ATM-Chk2 signaling pathway in naïve #28.3.25.13 cells. Interestingly, EVs derived from HBV-infected #28.3.25.13 cells included higher level of mitochondrial DNA (mtDNA) than those from HBV-infected #28.3.8 cells. Based on our results, we propose the novel model that EVs mediate the activation of ATM-Chk2 signaling pathway by the intercellular transfer of mtDNA in HBV-infected human hepatocyte.

Original languageEnglish
Pages (from-to)e21680
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume35
Issue number6
DOIs
Publication statusPublished - Jun 2021

Fingerprint

Dive into the research topics of 'Extracellular vesicles activate ATM-Chk2 signaling pathway through the intercellular transfer of mitochondrial DNA in HBV-infected human hepatocytes'. Together they form a unique fingerprint.

Cite this