title: Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog A/Akt pathway after middle cerebral artery occlusion in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.|Departments of neurology, Chongqing Medical University, Chongqing, China.
authors.forename: Xiping
authors.initials: X
authors.lastname: Liang
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: McBride
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Hetao
authors.initials: H
authors.lastname: Bian
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Spagnoli
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.|Departments of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D005455:Fluorescent Antibody Technique; D038702:Follistatin-Related Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D038702:Follistatin-Related Proteins; D034741:RNA, Small Interfering; C448719:Fstl1 protein, rat; D051057:Proto-Oncogene Proteins c-akt
keywords: apoptosis; follistatin-related proteins; infarction, middle cerebral artery