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Int J Clin Exp Pathol 2013;6(7):1282-1293

Original Article
Dynamic change of SGK expression and its role in neuron apoptosis after traumatic brain
injury

Xinmin Wu, Hui Mao, Jiao Liu, Jian Xu, Jianhua Cao, Xingxing Gu, Gang Cui

Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People’s Republic of China;
Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People’s Republic of China;
Department of Public Health, Nantong University, Nantong, Jiangsu Province 226001, People’s Republic of China; Affiliated mental health
centers of Nantong University, Nantong, Jiangsu Province 226001, People’s Republic of China; Key Laboratory of Neuroscience, Nantong
University, Nantong 226001, People’s Republic of China; Department of Neurosurgery, The First Affiliated Hospital of Soochow University,
Suzhou 215006, People’s Republic of China. Equal contributors.

Received April 15, 2013; Accepted May 20, 2013; Epub June 15, 2013; Published July 1, 2013

Abstract: Aims: Activation of specific signaling pathways in response to mechanical trauma causes delayed neuronal apoptosis; GSK-3β/β-
catenin signaling plays a critical role in the apoptosis of neurons in CNS diseases, SGK was discovered as a regulator of GSK-3β/β-catenin
pathway, The goal of this study was to determine if the mechanism of cell death or survival mediated by the SGK/GSK-3β/β-catenin pathway is
involved in a rat model of TBI. Main methods: Here, an acute traumatic brain injury model was applied to investigate the expression change and
possible roles of SGK, Expression of SGK, and total-GSK-3β, phospho-GSK3β on ser-9, beta-catenin, and caspase-3 were examined by
immunohistochemistry and Western blot analysis. Double immunofluorescent staining was used to observe the SGK localizations. Si-RNA
was performed to identify whether SGK regulates neuron apoptosis via GSK-3β/β-catenin pathway, ultimately inhibit caspase-3 activation. Key
findings: Temporally, SGK expression showed an increase pattern after TBI and reached a peak at day 3. Spatially, SGK was widely expressed
in the neuron, rarely in astrocytes and oligodendrocytes; in addition, the expression patterns of active caspase-3 and phospho-GSK3β were
parallel with that of SGK, at the same time, the expression of β-catenin shows similarity with SGK. In vitro, to further investigate the function of
SGK, a neuronal cell line PC12 was employed to establish an apoptosis model. We analyzed the association of SGK with apoptosis on PC12
cells by western blot, immunofluorescent labeling and siRNA. Significance: the results implied that SGK plays an important role in neuron
apoptosis via the regulation of GSK3β/β-catenin signaling pathway; ultimately inhibit caspase-3 activation. Taken together, we inferred
traumatic brain injury induced an upregulation of SGK in the central nervous system, which show a protective role in neuron apoptosis.
(IJCEP1304023).

Keywords: SGK, GSK3β/β-catenin signaling pathway, traumatic brain injury (TBI), neuron apoptosis

Address correspondence to: Xingxing Gu, Key Laboratory of Neuroscience, Nantong University, Nantong 226001, People’s Republic of China;
Gang Cui, Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China. E-
mail: cuigang@suda.edu.cn