title: Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.
abstract: OBJECTIVE
  To investigate the role of extracellular signal-regulated kinase1/2 (ERK1/2) pathway in the regulation of aquaporin 4 (AQP4) expression in cultured astrocytes after scratch-injury.
  
  
  METHODS
  The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase (LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2 (p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups.
  
  
  RESULTS
  Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury.
  
  
  CONCLUSIONS
  These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.
authors: Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: Zhong Fang
authors: ZF
authors: Shi
authors: Center for Neuroscience, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors: Wei Jiang
authors: WJ
authors: Zhao
authors: Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: Li Xin
authors: LX
authors: Xu
authors: Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: Li Ping
authors: LP
authors: Dong
authors: Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107-2699, USA.
authors: Shao Hua
authors: SH
authors: Yang
authors: Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: Fang
authors: F
authors: Yuan
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D002070:Butadienes / Q000008:administration & dosage; D002478:Cells, Cultured; D015536:Down-Regulation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009570:Nitriles / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000293:injuries*
chemical_list: D051401:Aquaporin 4; D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Aquaporin 4; Astrocytes; Extracellular signal-regulated kinases1/2; Scratch-injury