Mechanisms of resistance of hepatocyte retinoid X receptor alpha-null mice to WY-14,643-induced hepatocyte proliferation and cholestasis.

ABSTRACT: Peroxisome proliferators, such as the lipid-lowering fibrates that function as agonists for peroxisome proliferator-activated receptor alpha (PPARalpha), induce liver tumors in rodents and may produce cholestasis in humans. Considerable attention has focused on peroxisome proliferator-induced hepatocellular carcinoma, a phenomenon not noted in man, whereas limited studies examine fibrates and other therapeutic drugs that induce cholestasis, a common finding in humans. Moreover, the mechanisms by which fibrates induce hepatocyte proliferation and cholestasis are still not fully understood. We have examined the role of hepatocyte retinoid X receptor alpha (RXRalpha), an essential partner of PPARalpha, in modulating WY-14,643-induced hepatocyte proliferation and cholestasis. WY-14,643 treatme

SUBMITTER: Gyamfi MA 

PROVIDER: S-EPMC2666584 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature