title: TGF-β1/Smad3 Signaling Pathway Suppresses Cell Apoptosis in Cerebral Ischemic Stroke Rats.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Changshou City, Changshou, Jiangsu, China (mainland).
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Yancheng Third People's Hospital, The affiliated Yancheng Hospital of Southeast University Medical College, Yancheng, Jiangsu, China (mainland).
authors.forename: Qunfeng
authors.initials: Q
authors.lastname: Gui
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Hui
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).
authors.forename: Lianshu
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China (mainland).
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Yancheng Third People's Hospital, The affiliated Yancheng Hospital of Southeast University Medical College, Yancheng, Jiangsu, China (mainland).
authors.forename: Huaqun
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D020521:Stroke / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1