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TGF-β1/Smad3 Signaling Pathway Suppresses Cell Apoptosis in Cerebral Ischemic Stroke Rats

Haiping Zhu, Qunfeng Gui, Xiaobo Hui, Xiaodong Wang, Jian Jiang, Lianshu Ding, Xiaoyang Sun, Yanping Wang, Huaqun Chen

(Department of Neurosurgery, The First People’s Hospital of Changshou City, Changshou, Jiangsu, China (mainland))

Med Sci Monit 2017; 23:366-376

DOI: 10.12659/MSM.899195

Published: 2017-01-22


BACKGROUND: We desired to observe the changes of transforming growth factor-β1/drosophila mothers against decapentaplegic protein (TGF-β1/Smad3) signaling pathway in the hippocampus region of cerebral ischemic stroke rats so that the effects of this pathway on nerve cells can be investigated.
MATERIAL AND METHODS: The ischemic stroke models were built by middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro. TGF-β1 and TGF-β1 inhibitors were injected into rat models while TGF-β1, TGF-β1 siRNA, Smad3, and Smad3 siRNA were transfected into cells. Infarct sizes were measured using triphenyltetrazolium chloride (TTC) staining, while the apoptosis rate of cells were calculated by Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining. Levels of TGF-β1, Smad3, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR), immunohistochemical, and Western blot analysis.
RESULTS: The expressions of TGF-β1/Smad3 signal pathway were significantly increased in both model rats and BV2 cells, whereas the expression of Bcl-2 was down-regulated (P<0.05). The TGF-β1/Smad3 signal pathway exhibited protective effects, including the down-regulation of infarction size in cerebral tissues and the down-regulation of apoptosis rate of BV2 cells by increasing the expression of Bcl-2 (P<0.05). In addition, these effects could be antagonized by the corresponding inhibitors and siRNA (P<0.05).
CONCLUSIONS: The TGF-β1/Smad3 signaling pathway was up-regulated once cerebral ischemic stroke was simulated. TGF-β1 may activate the expression of Bcl-2 via Smad3 to suppress the apoptosis of neurons.

Keywords: Apoptosis, CA1 Region, Hippocampal, Genes, bcl-2, Infarction, Middle Cerebral Artery, Latent TGF-beta Binding Proteins, Smad Proteins



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