Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases½ Activation in Cultured Astrocytes Following Scratch-injury

Zhong Fang SHI, Wei Jiang ZHAO, Li Xin XU, Li Ping DONG, Shao Hua YANG, Fang YUAN

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Objective: To investigate the role of extracellular signal-regulated kinase½ (ERK½) 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-ERK½ (p-ERK½) expression was determined by Western blot. To explore the effect of ERK½ pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK½ 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 ERK½ activation. Furthermore, pretreatment with U0126 blocked both ERK½ activation and decrease in AQP4 expression induced by scratch-injury. Conclusion: These results indicate that ERK½ pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK½ pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.

Original languageEnglish
Pages (from-to)199-205
Number of pages7
JournalBiomedical and Environmental Sciences
Volume28
Issue number3
DOIs
StatePublished - Mar 2015

Keywords

  • Aquaporin 4
  • Astrocytes
  • Extracellular signal-regulated kinases½
  • Scratch-injury

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