Mechanical stretch induces TGF-β synthesis in hepatic stellate cells


  • Research Center for Innovative Cancer Therapy, Second Department of Medicine, Kurume University School of Medicine, Asahi-machi, Kurume (R. Sakata, T. Ueno, T. Nakamura, M. Sata); Department of Biochemistry and Molecular Pathophysiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan (H. Ueno), Japan.

Takato Ueno, MD, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830–0011, Japan. Tel.: +81–942–31–7746; fax: +81–942–31–7747; e-mail:


Background  It is known that mechanical stress induces extracellular matrix via transforming growth factor-β (TGF-β) synthesis in vascular smooth muscle cells. Activated hepatic stellate cells (HSCs) are an important source of TGF-β in the liver. However, it remains unclear whether mechanical stress induces TGF-β in HSCs. The Rho small GTP-binding protein (Rho) has recently emerged as an important regulator of actin and cytoskeleton. We examined whether TGF-β is expressed in stretched HSCs and whether Rho is involved in stretch-induced TGF-β synthesis.

Materials and methods  A cultured human HSC cell line, LI90, was used for this study. Hepatic stellate cells were cyclically stretched using the Flexercell® strain unit. Concentration of TGF-β in the conditioned medium was estimated by a bioassay using mink lung epithelial cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct. Transforming growth factor-β mRNA expression of HSCs was estimated by a reverse-transcription polymerase chain reaction. Replication-defective adenoviral vectors expressing a dominant negative type of Rho was utilized to suppress its effect on HSCs.

Results  Transforming growth factor-β concentration of the conditioned media of stretched HSCs showed time-dependent increases as compared to nonstretched HSCs from 2 h to 24 h. Transforming growth factor-β mRNA expression in stretched HSCs was increased compared with that in nonstretched HSCs. Transfection of dominant negative Rho inhibited the stretch-induced TGF-β synthesis.

Conclusions  Mechanical stretch enhanced TGF-β expression on mRNA and protein level in HSCs. Rho was closely related to stretch-induced TGF-β synthesis in HSCs.