Xin-Guo Li1, Yi-Bao Wang1. 1. Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, China.
Abstract
OBJECTIVE: Intracranial aneurysm (IA) is a life threatening cerebrovascular disease characterized by phenotypic modulation of vascular smooth muscle cells (VSMCs) and loss of vessel cells. In addition to environmental factors, genetic factors have been proposed to be a critical factor in the onset and progression of IA. The present study investigates the effects of serine-arginine protein kinase 1 (SRPK1) on VSMC proliferation and apoptosis both in vivo and in vitro, as well as its role in vascular remodeling in vivo through PI3 K/Akt signaling in IA. METHODS: Differentially expressed genes related to IA were initially identified using microarray analysis. Immunohistochemistry was conducted to determine SRPK1 expression in the vascular walls in IA and normal cerebral vascular walls. TUNEL staining were applied to observe cell apoptosis patterns of VSMCs. VSMC proliferation and apoptosis in vitro were detected by cell counting kit-8 (CCK8) assay and flow cytometry. The expressions of SRPK1, PI3 K/Akt signaling pathway- and apoptosis-related genes were evaluated by RT-qPCR and Western blot analysis. RESULTS: Microarray data of GSE36791 and GSE54083 were analyzed to determine the selection of SRPK1 gene. The vascular walls in IA rat models produced high levels of SRPK1 expression and an activated PI3 K/Akt signaling pathway. VSMCs treated with siRNA-SRPK1 exhibited enhanced cell proliferation, repressed cell apoptosis, and increased vascular remodeling, all of which suggest the inhibition of the PI3 K/AKT pathway. Notably, PI3 K/AKT pathway reversed the effect of SRPK1 silencing. CONCLUSION: Our results show that siRNA-mediated silencing of SRPK1 gene inhibits VSMC apoptosis, and increases VSMCs proliferation and vascular remodeling in IA via the PI3 K/Akt signaling pathway. Our findings provide a novel intervention target for the molecular treatment of IA.
OBJECTIVE:Intracranial aneurysm (IA) is a life threatening cerebrovascular disease characterized by phenotypic modulation of vascular smooth muscle cells (VSMCs) and loss of vessel cells. In addition to environmental factors, genetic factors have been proposed to be a critical factor in the onset and progression of IA. The present study investigates the effects of serine-arginine protein kinase 1 (SRPK1) on VSMC proliferation and apoptosis both in vivo and in vitro, as well as its role in vascular remodeling in vivo through PI3 K/Akt signaling in IA. METHODS: Differentially expressed genes related to IA were initially identified using microarray analysis. Immunohistochemistry was conducted to determine SRPK1 expression in the vascular walls in IA and normal cerebral vascular walls. TUNEL staining were applied to observe cell apoptosis patterns of VSMCs. VSMC proliferation and apoptosis in vitro were detected by cell counting kit-8 (CCK8) assay and flow cytometry. The expressions of SRPK1, PI3 K/Akt signaling pathway- and apoptosis-related genes were evaluated by RT-qPCR and Western blot analysis. RESULTS: Microarray data of GSE36791 and GSE54083 were analyzed to determine the selection of SRPK1 gene. The vascular walls in IA rat models produced high levels of SRPK1 expression and an activated PI3 K/Akt signaling pathway. VSMCs treated with siRNA-SRPK1 exhibited enhanced cell proliferation, repressed cell apoptosis, and increased vascular remodeling, all of which suggest the inhibition of the PI3 K/AKT pathway. Notably, PI3 K/AKT pathway reversed the effect of SRPK1 silencing. CONCLUSION: Our results show that siRNA-mediated silencing of SRPK1 gene inhibits VSMC apoptosis, and increases VSMCs proliferation and vascular remodeling in IA via the PI3 K/Akt signaling pathway. Our findings provide a novel intervention target for the molecular treatment of IA.
Authors: Sebastian Oltean; Melissa Gammons; Richard Hulse; Maryam Hamdollah-Zadeh; Athina Mavrou; Lucy Donaldson; Andrew H Salmon; Steve J Harper; Michael R Ladomery; David O Bates Journal: Biochem Soc Trans Date: 2012-08 Impact factor: 5.407
Authors: Vincent M Tutino; Hamidreza Rajabzadeh-Oghaz; Sricharan S Veeturi; Kerry E Poppenberg; Muhammad Waqas; Max Mandelbaum; Nicholas Liaw; Adnan H Siddiqui; Hui Meng; John Kolega Journal: Neurosurg Rev Date: 2021-01-26 Impact factor: 2.800