Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog A/Akt pathway after middle cerebral artery occlusion in rats

Xiping Liang, Qin Hu, Bo Li, Devin McBride, Hetao Bian, Pierre Spagnoli, Di Chen, Jiping Tang, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND AND PURPOSE -: Follistatin-like 1 (FSTL1), an extracellular glycoprotein, has been reported to decrease apoptosis in ischemic cardiac diseases, but its effect in ischemic stroke has not been examined. We hypothesized that recombinant FSTL1 attenuates neuronal apoptosis through its receptor disco-interacting protein 2 homolog A (DIP2A) and the Akt pathway after middle cerebral artery occlusion (MCAO) in rats. METHODS -: One hundred forty male Sprague-Dawley rats were subjected to 2 hours of MCAO followed by reperfusion. In a subset of animals, the time course and location of FSTL1 and DIP2A were detected by Western blot and immunofluorescence double staining. Another set of animals were intracerebroventricularly given either recombinant FSTL1 1 hour after reperfusion or FSTL1-small interfering RNA (siRNA) 48 hours before reperfusion. Additionally, DIP2A was knockdown by siRNA in some animals. Infarction volume and neurological deficits were measured, and the expression of FSTL1, DIP2A, phosphorylated Akt, cleaved caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling were quantified using Western blot. RESULTS -: The expression of FSTL1 and DIP2A was increased in neurons and peaked 24 hours after MCAO. Recombinant FSTL1 reduced brain infarction and improved neurological deficits 24 and 72 hours after MCAO via activation of its receptor DIP2A and downstream phosphorylation of Akt. These effects were reversed by DIP2A-siRNA and FSTL1-siRNA. CONCLUSIONS -: Recombinant FSTL1 decreases neuronal apoptosis and improves neurological deficits through phosphorylation of Akt by activation of its receptor DIP2A after MCAO in rats. Thus, FSTL1 may have potentials as a treatment for patients with ischemic stroke.

Original languageEnglish
Pages (from-to)3048-3054
Number of pages7
JournalStroke
Volume45
Issue number10
DOIs
StatePublished - Oct 12 2014

ASJC Scopus Subject Areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Keywords

  • apoptosis
  • follistatin-related proteins
  • infarction
  • middle cerebral artery
  • In Situ Nick-End Labeling
  • Cell Survival/physiology
  • Rats
  • Male
  • Proto-Oncogene Proteins c-akt/metabolism
  • Rats, Sprague-Dawley
  • Blotting, Western
  • Gene Knockdown Techniques
  • Signal Transduction/physiology
  • Follistatin-Related Proteins/metabolism
  • Animals
  • Apoptosis/physiology
  • Neurons/metabolism
  • Fluorescent Antibody Technique
  • Infarction, Middle Cerebral Artery/metabolism
  • RNA, Small Interfering
  • Reperfusion Injury/metabolism

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