Carcinogenesis Advance Access published online on September 26, 2003
Carcinogenesis, doi:10.1093/carcin/bgg180
© 2003 by Oxford University Press
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CARCINOGENESIS
1 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison WI 53706
* Corresponding author. E-mail: sandgren{at}svm.vetmed.wisc.edu.
Received 14 March 2003
; revised 2 September 2003
; accepted 12 September 2003
Peroxisome proliferator activated receptor
cell autonomous, chimeric liver, hepatocyte transplantation, peroxisome proliferator, transgenic mice
Cell cross-talk mediates PPAR
-null hepatocyte proliferation after peroxisome proliferator exposure
(PPAR
) mediates the liver's responses to peroxisome proliferator compounds. These responses include induction of specific hepatic enzymes, peroxisome proliferation, and hepatocyte proliferation. PPAR
null mice, which lack receptor in all cells of the body, do not respond to peroxisome proliferators, indicating that hepatocellular proliferation and other responses require the presence of this receptor in at least some cells. To determine if PPAR
is required specifically in hepatocytes for each response, we used hepatocyte transplantation to generate chimeric livers composed of PPAR
null and positive hepatocytes in PPAR
null or positive hosts. Upon exposure to a peroxisome proliferator, peroxisome proliferation and enzyme induction were restricted to receptor positive hepatocytes, indicating that these responses are cell autonomous with respect to hepatocyte receptor status. However, both PPAR
null and positive hepatocytes in chimeric livers displayed elevated DNA synthesis regardless of host receptor status, as long as at least some hepatocytes contained receptor. These findings indicate that the mitogenic response to peroxisome proliferators does not require PPAR
in all hepatocytes.![]()
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