Extracellular vesicles activate ATM‐Chk2 signaling pathway through the intercellular transfer of mitochondrial DNA in HBV‐infected human hepatocytes. Issue 6 (27th May 2021)

• Record Type: Journal Article
• Authors: Dansako, Hiromichi; Ueda, Youki; Satoh, Shinya; Kato, Nobuyuki
• Is Part Of: FASEB journal. Volume 35:Issue 6(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-27
• Subjects: ATM‐Chk2 signaling pathway -- extracellular vesicles -- hepatitis B virus -- mitochondrial DNA; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202002678R
• Languages: English
• ISSNs: 0892-6638

Abstract

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.