Inhibition of GSK-3beta decreases NF-kappaB-dependent gene expression and impairs the rat liver regeneration.

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.

Chen H ，Yang S ，Yang Z ，Ma L ，Jiang D ，Mao J ，Jiao B ，Cai Z ... -  《JOURNAL OF CELLULAR BIOCHEMISTRY》

Inhibition of GSK-3beta ameliorates hepatic ischemia-reperfusion injury through GSK-3beta/beta-catenin signaling pathway in mice.

Xia YX ，Lu L ，Wu ZS ，Pu LY ，Sun BC ，Wang XH ... -  《Hepatobiliary & Pancreatic Diseases International》

GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway.

Ji XK ，Xie YK ，Zhong JQ ，Xu QG ，Zeng QQ ，Wang Y ，Zhang QY ，Shan YF ... -  《-》

Inhibiting glycogen synthase kinase 3beta in sepsis.

Dugo L ，Collin M ，Allen DA ，Patel NS ，Bauer I ，Mervaala E ，Louhelainen M ，Foster SJ ，Yaqoob MM ，Thiemermann C ... -  《-》

GSK-3beta inhibitors attenuate the organ injury/dysfunction caused by endotoxemia in the rat.

Dugo L ，Collin M ，Allen DA ，Patel NS ，Bauer I ，Mervaala EM ，Louhelainen M ，Foster SJ ，Yaqoob MM ，Thiemermann C ... -  《-》