Xiping Liang1,2, Qin Hu1, Bo Li1, Devin McBride1, Hetao Bian1, Pierre Spagnoli1, Di Chen1, Jiping Tang1, John H Zhang1,3. 1. Departments of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA. 2. Departments of neurology, Chongqing Medical University, Chongqing, China. 3. Departments of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA, USA.
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.
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 FSTL1decreases 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: Enrique Lara-Pezzi; Leanne E Felkin; Emma J Birks; Padmini Sarathchandra; Kalyani D Panse; Robert George; Jennifer L Hall; Magdi H Yacoub; Nadia Rosenthal; Paul J R Barton Journal: Endocrinology Date: 2008-07-10 Impact factor: 4.736
Authors: Queeny K Y Chan; Hextan Y S Ngan; Philip P C Ip; Vincent W S Liu; W C Xue; Annie N Y Cheung Journal: Carcinogenesis Date: 2008-09-16 Impact factor: 4.944
Authors: Mengjie Wu; Yongfeng Ding; Nan Wu; Junjie Jiang; Yingying Huang; Fanyu Zhang; Haiyong Wang; Quan Zhou; Yan Yang; Wei Zhuo; Lisong Teng Journal: Am J Cancer Res Date: 2021-03-01 Impact factor: 6.166
Authors: Matthew Henkel; Jessica Partyka; Alyssa D Gregory; Erick Forno; Michael H Cho; Taylor Eddens; Andrew R Tout; Nathan Salamacha; William Horne; Krithika S Rao; Yijen Wu; John F Alcorn; Dennis Kostka; Raphael Hirsch; Juan C Celedón; Steven D Shapiro; Jay K Kolls; Brian T Campfield Journal: Am J Respir Crit Care Med Date: 2020-04-15 Impact factor: 21.405