TY - JOUR
T1 - Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes
AU - Qin, Xian Yang
AU - Hara, Mitsuko
AU - Arner, Erik
AU - Kawaguchi, Yoshikuni
AU - Inoue, Ikuyo
AU - Tatsukawa, Hideki
AU - Furutani, Yutaka
AU - Nagatsuma, Keisuke
AU - Matsuura, Tomokazu
AU - Wei, Feifei
AU - Kikuchi, Jun
AU - Sone, Hideko
AU - Daub, Carsten
AU - Kawaji, Hideya
AU - Lassmann, Timo
AU - Itoh, Masayoshi
AU - Suzuki, Harukazu
AU - Carninci, Piero
AU - Hayashizaki, Yoshihide
AU - Kokudo, Norihiro
AU - Forrest, Alistair R.R.
AU - Kojima, Soichi
AU - The FANTOM Consortium
PY - 2017/10/1
Y1 - 2017/10/1
N2 - The acute phase protein orosomucoid-1 (Orm1) is mainly expressed by hepatocytes (HPCs) under stress conditions. However, its specific function is not fully understood. Here, we report a role of Orm1 as an executer of HPC proliferation. Increases in serum levels of Orm1 were observed in patients after surgical resection for liver cancer and in mice undergone partial hepatectomy (PH). Transcriptome study showed that Orm1 became the most abundant in HPCs isolated from regenerating mouse liver tissues after PH. Both in vitro and in vivo siRNA-induced knockdown of Orm1 suppressed proliferation of mouse regenerating HPCs and human hepatic cells. Microarray analysis in regenerating mouse livers revealed that the signaling pathways controlling chromatin replication, especially the minichromosome maintenance protein complex genes were uniformly down-regulated following Orm1 knockdown. These data suggest that Orm1 is induced in response to hepatic injury and executes liver regeneration by activating cell cycle progression in HPCs.
AB - The acute phase protein orosomucoid-1 (Orm1) is mainly expressed by hepatocytes (HPCs) under stress conditions. However, its specific function is not fully understood. Here, we report a role of Orm1 as an executer of HPC proliferation. Increases in serum levels of Orm1 were observed in patients after surgical resection for liver cancer and in mice undergone partial hepatectomy (PH). Transcriptome study showed that Orm1 became the most abundant in HPCs isolated from regenerating mouse liver tissues after PH. Both in vitro and in vivo siRNA-induced knockdown of Orm1 suppressed proliferation of mouse regenerating HPCs and human hepatic cells. Microarray analysis in regenerating mouse livers revealed that the signaling pathways controlling chromatin replication, especially the minichromosome maintenance protein complex genes were uniformly down-regulated following Orm1 knockdown. These data suggest that Orm1 is induced in response to hepatic injury and executes liver regeneration by activating cell cycle progression in HPCs.
KW - Bioinformatics
KW - Cell cycle
KW - Hepatocyte proliferation
KW - Lipocalin
KW - Orosomucoid-1
UR - http://www.scopus.com/inward/record.url?scp=85029535903&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2017.09.008
DO - 10.1016/j.ebiom.2017.09.008
M3 - Article
C2 - 28927749
AN - SCOPUS:85029535903
SN - 2352-3964
VL - 24
SP - 257
EP - 266
JO - EBioMedicine
JF - EBioMedicine
ER -
