Journal Article

Cell cross-talk mediates PPARα null hepatocyte proliferation after peroxisome proliferator exposure

Teresa C. Weglarz and Eric P. Sandgren

in Carcinogenesis

Volume 25, issue 1, pages 107-112
Published in print January 2004 | ISSN: 0143-3334
Published online January 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg180
Cell cross-talk mediates PPARα null hepatocyte proliferation after peroxisome proliferator exposure

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Peroxisome proliferator activated receptorα (PPARα) mediates the liver's responses to peroxisome proliferator compounds. These responses include induction of specific hepatic enzymes, peroxisome proliferation and hepatocyte proliferation. PPARα 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 PPARα is required specifically in hepatocytes for each response, we used hepatocyte transplantation to generate chimeric livers composed of PPARα null and positive hepatocytes in PPARα 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 PPARα 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 PPARα in all hepatocytes.

Keywords: L-PBE, peroxisomal L-bifunctional enzyme; NPC, non-parenchymal cell; PPARα, peroxisome proliferator associated receptor alpha; TNFα, tumor necrosis factor alpha; uPA, urokinase-type plasminogen activator

Journal Article.  3690 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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