Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes

Xian Yang Qin, Mitsuko Hara, Erik Arner, Yoshikuni Kawaguchi, Ikuyo Inoue, Hideki Tatsukawa, Yutaka Furutani, Keisuke Nagatsuma, Tomokazu Matsuura, Feifei Wei, Jun Kikuchi, Hideko Sone, Carsten Daub, Hideya Kawaji, Timo Lassmann, Masayoshi Itoh, Harukazu Suzuki, Piero Carninci, Yoshihide Hayashizaki, Norihiro KokudoAlistair R.R. Forrest, Soichi Kojima, The FANTOM Consortium

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)257-266
Number of pages10
JournalEBioMedicine
Volume24
DOIs
Publication statusPublished - 1 Oct 2017

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