Effects of rapamycin on cultured hepatocyte proliferation and gene expression

Antonio Francavilla, Brian I. Carr, Thomas E. Starzl, Alessandro Azzarone, Giuseppe Carrieri, Qui Hua Zeng

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Rapamycin, a potent immunosuppressive drug that disrupts normal signal-transduction processes, inhibited hepatocyte proliferation without evidence of inherent cytotoxicity in rat hepatocytes cultured in conventional medium or in a medium enriched with epidermal growth factor. The antiproliferative effect was dose dependent, uninfluenced by the concentration of epidermal growth factor in the medium and long lasting after a brief exposure. The effect of rapamycin was unaltered by the concomitant presence of FK 506 in the medium, suggesting that different binding affinities of these two drugs or even a separate rapamycin binding site may exist. Hepatocytes harvested 12 and 24 hr after partial hepatectomy were progressively less responsive to the antiproliferative effect of rapamycin. The gene expression of transforming growth factor-β was reduced under in vivo rapamycin treatment, but at the same time the gene expression of albumin and glyceraldehyde-3-phosphate dehydrogenase was unchanged or increased. The experiments confirm that rapamycin has inherent growth-control qualities, and they strengthen the hypothesis that the recently defined immunophilin network is central to many aspects of cellular growth control.

Original languageEnglish
Pages (from-to)871-877
Number of pages7
JournalHepatology
Volume15
Issue number5
Publication statusPublished - May 1992

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Sirolimus
Hepatocytes
Gene Expression
Epidermal Growth Factor
Immunophilins
Glyceraldehyde-3-Phosphate Dehydrogenases
Hepatectomy
Transforming Growth Factors
Tacrolimus
Immunosuppressive Agents
Growth
Quality Control
Pharmaceutical Preparations
Albumins
Signal Transduction
Binding Sites

ASJC Scopus subject areas

  • Hepatology

Cite this

Francavilla, A., Carr, B. I., Starzl, T. E., Azzarone, A., Carrieri, G., & Zeng, Q. H. (1992). Effects of rapamycin on cultured hepatocyte proliferation and gene expression. Hepatology, 15(5), 871-877.

Effects of rapamycin on cultured hepatocyte proliferation and gene expression. / Francavilla, Antonio; Carr, Brian I.; Starzl, Thomas E.; Azzarone, Alessandro; Carrieri, Giuseppe; Zeng, Qui Hua.

In: Hepatology, Vol. 15, No. 5, 05.1992, p. 871-877.

Research output: Contribution to journalArticle

Francavilla, A, Carr, BI, Starzl, TE, Azzarone, A, Carrieri, G & Zeng, QH 1992, 'Effects of rapamycin on cultured hepatocyte proliferation and gene expression', Hepatology, vol. 15, no. 5, pp. 871-877.
Francavilla A, Carr BI, Starzl TE, Azzarone A, Carrieri G, Zeng QH. Effects of rapamycin on cultured hepatocyte proliferation and gene expression. Hepatology. 1992 May;15(5):871-877.
Francavilla, Antonio ; Carr, Brian I. ; Starzl, Thomas E. ; Azzarone, Alessandro ; Carrieri, Giuseppe ; Zeng, Qui Hua. / Effects of rapamycin on cultured hepatocyte proliferation and gene expression. In: Hepatology. 1992 ; Vol. 15, No. 5. pp. 871-877.
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