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Effects of rapamycin on cultured hepatocyte proliferation and gene expression

Francavilla, A and Carr, BI and Starzl, TE and Azzarone, A and Carrieri, G and Zeng, Q (1992) Effects of rapamycin on cultured hepatocyte proliferation and gene expression. Hepatology, 15 (5). 871 - 877. ISSN 0270-9139

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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. (HEPATOLOGY 1992;15:871–877). Copyright © 1992 American Association for the Study of Liver Diseases


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Francavilla, A
Carr, BI
Starzl, TEtes11@pitt.eduTES11
Azzarone, A
Carrieri, G
Zeng, Q
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1992
Date Type: Publication
Journal or Publication Title: Hepatology
Volume: 15
Number: 5
Page Range: 871 - 877
DOI or Unique Handle: 10.1002/hep.1840150520
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0270-9139
Other ID: uls-drl:31735062111392, Starzl CV No. 1345
Date Deposited: 08 Apr 2010 17:22
Last Modified: 13 Oct 2017 21:56
URI: http://d-scholarship.pitt.edu/id/eprint/4731

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