KMID : 0606920170250050504
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Biomolecules & Therapeutics 2017 Volume.25 No. 5 p.504 ~ p.510
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Nuclear Receptor PPAR¥á Agonist Wy-14,643 Ameliorates Hepatic Cell Death in Hepatic IKK¥â-Deficient Mice
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Kim Tae-Hyeong
Wahyudi Lilik Duwi Gonzalez Frank J. Kim Jung-Hwan
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Abstract
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Inhibitor of nuclear factor kappa-B kinase beta (IKK¥â) plays a critical role in cell proliferation and inflammation in various cells by activating NF-¥êB signaling. However, the interrelationship between peroxisome proliferator-activated receptor ¥á (PPAR¥á) and IKK¥â in cell proliferation is not clear. In this study, we investigated the possible role of PPAR¥á in the hepatic cell death in the absence of IKK¥â gene using liver-specific Ikkb-null (IkkbF/F-AlbCre) mice. To examine the function of PPAR¥á activation in hepatic cell death, wild-type (IkkbF/F) and IkkbF/F-AlbCre mice were treated with PPAR¥á agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the IkkbF/F-AlbCre mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and IkkbF/F-AlbCre mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that IKK¥â-derived hepatic apoptosis could be altered by PPAR¥á activation in conjunction with activation of NF-¥êB and STAT3 signaling.
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KEYWORD
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PPARa, IKKb, NF-kB, Wy-14, 643, STAT3
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