title: Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis.
abstract: Primary biliary cirrhosis (PBC) is one of the most important autoimmune liver diseases but the etiology and pathogenesis remain unknown. In this study, we analyzed differential mRNA expression in the liver of a patient with PBC using suppression subtractive hybridization to identify overexpressed genes. Overexpression of mRNA transcripts from mitochondrial DNA was observed in the PBC liver, compared to normal liver. To explore the mechanism of increased mitochondrial transcription, we investigated the mRNA levels of nuclear DNA-encoded regulator molecules of mitochondrial gene expression in 60 liver biopsy samples from various diseases, including PBC, using competitive RT-PCR. Increased expression of mitochondrial transcriptional factor A (mtTFA) and mitochondrial nuclear respiratory factor 1 (NRF-1) mRNA was demonstrated in PBC liver compared to other liver diseases, while NRF-1 coactivator 1, PGC-1 was suppressed. Mitochondrial DNA-encoded mRNA molecules are overexpressed in the PBC liver, and this is associated with up-regulation of mitochondrial transcription factor mtTFA and its transactivator NRF-1. Further studies are needed to focus on the relevance of this perturbation of mitochondrial gene expression in the pathogenesis of PBC.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
authors.forename: Cheng-Hsin
authors.initials: CH
authors.lastname: Chen
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Nagayama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Miyasaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Maekawa
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Chifumi
authors.initials: C
authors.lastname: Sato
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe