title: Mechanical stretch induces matrix metalloproteinase 1 production in human hepatic stellate cells.
abstract: In increasing portal blood flow, hepatic stellate cells (HSC) may be lengthened in response to mechanical stretch stimulation and their function may be changed. However, little is known about the influence of mechanical stretch on hepatic stellate cells. We examined production of matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), and extracellular matrix by hepatic stellate cells to investigate the relationship between mechanical stretch and hepatic fibrosis. LI90 cells, human hepatic stellate cells, were stretched cyclically using the Flexer cell strain unit. Concentrations of MMP1, MMP2, TIMP1, TIMP2, type I collagen C-telopeptide (1CTP), procollagen III propeptide (PIIIP), and hyaluronic acid in culture supernatants were determined. MMP1, MMP2, and TIMP1 mRNA expression was measured by reverse transcription-polymerase chain reaction (RT-PCR). In stretched LI90 cells, concentration of MMP1 showed an increase relative to unstretched cells, but concentrations of MMP2, TIMPl, and TIMP2 showed a decrease. MMP1/TIMP1 ratio and MMP1 mRNA expression showed an increase in stretched cells. Our finding suggested that in the early phase of portal hypertension, hepatic stellate cells increase production of MMPl and decrease production of TIMP1 and TIMP2, activated by mechanical stretch.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Goto
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Mikami
authors.forename: Kouich
authors.initials: K
authors.lastname: Miura
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ohshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yoneyama
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakane
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe