Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells

M. Nakamuta, Motoyuki Kohjima, M. Fukushima, S. Morizono, K. Kotoh, N. Kobayashi, M. Enjoji

Research output: Contribution to journalArticle

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Abstract

Background. In HCV-related graft hepatitis, immunosuppression has been implicated in rapid progression to cirrhosis, a serious clinical issue. We investigated the effects of cyclosporine or tacrolimus on cell growth and collagen production by hepatic stellate cells (HSC), which play a role in hepatic fibrosis. Materials and methods. Cultured rat HSCs and human HSC-derived TWNT-4 cells were evaluated for proliferation, type I collagen, phosphorylation states of mitogen-activated protein kinases extracellular signal-regulated kinase 1/2; [MAPKs Erk1/2], c-Jun N-terminal kinase (JNK, p38), as well as the expression of collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) genes. Results. Cyclosporine suppressed cell growth and collagen production in a concentration-dependent manner. At clinically relevant concentrations of 0.125 μmol (150 ng/mL) cyclosporine significantly reduced collagen production per cell by more than 50%. Similarly, tacrolimus also reduced both collagen concentration and cell number; however, tacrolimus at a clinically relevant concentration of 12.5 nmol (10 ng/mL) did not significantly reduce collagen production. Treatment with cyclosporine reduced type I collagen and TIMP-1 expression and enhanced MMP-1 expression. Cyclosporine also inhibited phosphorylation strongly for JNK and p38, and weakly inhibited for Erk1/2. Conclusion. These findings demonstrated that cyclosporine suppresses cell growth and collagen production, suggesting that it may have an antifibrogenic effect.

Original languageEnglish
Pages (from-to)4598-4602
Number of pages5
JournalTransplantation Proceedings
Volume37
Issue number10
DOIs
Publication statusPublished - Dec 1 2005

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Hepatic Stellate Cells
Cyclosporine
Collagen
Matrix Metalloproteinase 1
Growth
Tacrolimus
Tissue Inhibitor of Metalloproteinase-1
Collagen Type I
Fibrosis
Phosphorylation
Matrix Metalloproteinase Inhibitors
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinases
Immunosuppression
Hepatitis
Cell Count
Transplants
Liver

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

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Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells. / Nakamuta, M.; Kohjima, Motoyuki; Fukushima, M.; Morizono, S.; Kotoh, K.; Kobayashi, N.; Enjoji, M.

In: Transplantation Proceedings, Vol. 37, No. 10, 01.12.2005, p. 4598-4602.

Research output: Contribution to journalArticle

Nakamuta, M, Kohjima, M, Fukushima, M, Morizono, S, Kotoh, K, Kobayashi, N & Enjoji, M 2005, 'Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells', Transplantation Proceedings, vol. 37, no. 10, pp. 4598-4602. https://doi.org/10.1016/j.transproceed.2005.10.104
Nakamuta, M. ; Kohjima, Motoyuki ; Fukushima, M. ; Morizono, S. ; Kotoh, K. ; Kobayashi, N. ; Enjoji, M. / Cyclosporine suppresses cell growth and collagen production in hepatic stellate cells. In: Transplantation Proceedings. 2005 ; Vol. 37, No. 10. pp. 4598-4602.
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