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Chen H, Yang S, Yang Z, Ma L, Jiang D, Mao J, Jiao B, Cai Z: Inhibition of GSK-3beta decreases NF-kappaB-dependent gene expression and impairs the rat liver regeneration. J Cell Biochem. 2007 Dec 1;102(5):1281-9.
Serine-threonine protein kinase glycogen synthase kinase (GSK)-3 is involved in regulation of many cell functions, but its role in regulating liver regeneration is unknown. Here we investigated the effects of GSK-3beta inhibition on liver regeneration after partial hepatectomy in the rat. The potent and selective GSK-3beta inhibitor SB216763 (0.6 mg/kg intravenously) or vehicle (10% dimethyl sulfoxide) was administered 30 min before 70% partial hepatectomy. Liver regeneration was estimated by the cell proliferation, apoptosis, and the related cell signaling and cycling proteins. In 30 min after hepatectomy in the rat, GSK-3beta was found to be translocated to the nucleus, but GSK-3beta inhibitor SB216763 that could phosphorylate residue Ser9 on GSK-3beta did not attenuated the accumulation. Consequently, the inhibition of GSK-3beta decreased the nuclear factor-kappaB activity, the NF-kappaB-dependent gene expression, and COX2 expression, but enhanced p21 (WAF1/Cip1) transcription. Moreover, the injection of SB216763 impaired the proliferation cell nuclear antigen (PCNA) index and increased the apoptosis of liver compared to the vehicle. GSK-3beta plays an important role in rat liver regeneration. We conclude it may partially result from the inhibition of the NF-kappaB pathway and enhancement of p21 (WAF1/Cip1) expression. |
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