Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis.
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.
Chen
Cheng-Hsin
CH
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan.
Nagayama
Kazuyoshi
K
Enomoto
Nobuyuki
N
Miyasaka
Yuka
Y
Kurosaki
Masayuki
M
Sakamoto
Naoya
N
Maekawa
Shinya
S
Kakinuma
Sei
S
Ikeda
Takaaki
T
Izumi
Namiki
N
Sato
Chifumi
C
Watanabe
Mamoru
M