Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis

J. Zhu, J. Wu, E. Frizell, S. L. Liu, R. Bashey, R. Rubin, P. Norton, Mark A Zern

Research output: Contribution to journalArticle

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Abstract

Background and Aims: The accelerated course of hepatic fibrosis that occurs in some patients after liver transplantation is a major clinical problem. This response may be caused by the antirejection therapeutics, and in an earlier report we showed that FK-506 enhanced the fibrogenic process in in vivo and in vitro models of liver fibrosis. In the present study, the aim was to determine whether a new immunosuppressive agent, rapamycin, enhances or inhibits liver fibrosis. Methods: Effects of rapamycin were investigated in a carbon tetrachloride model of hepatic fibrosis in rats and on hepatic stellate proliferation in vitro. Results: Rapamycin inhibited extracellular matrix deposition in the rat model of fibrogenesis as determined by histological analysis, collagen content, messenger RNA levels of procollagen and transforming growth factor β1, and tissue transglutaminase activity. Moreover, rapamycin decreased platelet growth factor-induced proliferation of hepatic stellate cells. Conclusions: These findings indicate that the new antirejection agent rapamycin inhibits hepatic fibrosis and thus may become a valuable addition to the immunosuppression armamentarium.

Original languageEnglish (US)
Pages (from-to)1198-1204
Number of pages7
JournalGastroenterology
Volume117
Issue number5
DOIs
StatePublished - 1999

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Hepatic Stellate Cells
Sirolimus
Liver Cirrhosis
Cell Proliferation
Fibrosis
Liver
Procollagen
Carbon Tetrachloride
Transforming Growth Factors
Tacrolimus
Immunosuppressive Agents
Liver Transplantation
Immunosuppression
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Collagen
Blood Platelets
In Vitro Techniques
Messenger RNA

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis. / Zhu, J.; Wu, J.; Frizell, E.; Liu, S. L.; Bashey, R.; Rubin, R.; Norton, P.; Zern, Mark A.

In: Gastroenterology, Vol. 117, No. 5, 1999, p. 1198-1204.

Research output: Contribution to journalArticle

Zhu, J. ; Wu, J. ; Frizell, E. ; Liu, S. L. ; Bashey, R. ; Rubin, R. ; Norton, P. ; Zern, Mark A. / Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis. In: Gastroenterology. 1999 ; Vol. 117, No. 5. pp. 1198-1204.
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AU - Zhu, J.

AU - Wu, J.

AU - Frizell, E.

AU - Liu, S. L.

AU - Bashey, R.

AU - Rubin, R.

AU - Norton, P.

AU - Zern, Mark A

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N2 - Background and Aims: The accelerated course of hepatic fibrosis that occurs in some patients after liver transplantation is a major clinical problem. This response may be caused by the antirejection therapeutics, and in an earlier report we showed that FK-506 enhanced the fibrogenic process in in vivo and in vitro models of liver fibrosis. In the present study, the aim was to determine whether a new immunosuppressive agent, rapamycin, enhances or inhibits liver fibrosis. Methods: Effects of rapamycin were investigated in a carbon tetrachloride model of hepatic fibrosis in rats and on hepatic stellate proliferation in vitro. Results: Rapamycin inhibited extracellular matrix deposition in the rat model of fibrogenesis as determined by histological analysis, collagen content, messenger RNA levels of procollagen and transforming growth factor β1, and tissue transglutaminase activity. Moreover, rapamycin decreased platelet growth factor-induced proliferation of hepatic stellate cells. Conclusions: These findings indicate that the new antirejection agent rapamycin inhibits hepatic fibrosis and thus may become a valuable addition to the immunosuppression armamentarium.

AB - Background and Aims: The accelerated course of hepatic fibrosis that occurs in some patients after liver transplantation is a major clinical problem. This response may be caused by the antirejection therapeutics, and in an earlier report we showed that FK-506 enhanced the fibrogenic process in in vivo and in vitro models of liver fibrosis. In the present study, the aim was to determine whether a new immunosuppressive agent, rapamycin, enhances or inhibits liver fibrosis. Methods: Effects of rapamycin were investigated in a carbon tetrachloride model of hepatic fibrosis in rats and on hepatic stellate proliferation in vitro. Results: Rapamycin inhibited extracellular matrix deposition in the rat model of fibrogenesis as determined by histological analysis, collagen content, messenger RNA levels of procollagen and transforming growth factor β1, and tissue transglutaminase activity. Moreover, rapamycin decreased platelet growth factor-induced proliferation of hepatic stellate cells. Conclusions: These findings indicate that the new antirejection agent rapamycin inhibits hepatic fibrosis and thus may become a valuable addition to the immunosuppression armamentarium.

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