Induction of SPARC on Oxidative Stress, Inflammatory Phenotype Transformation, and Apoptosis of Human Brain Smooth Muscl
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Induction of SPARC on Oxidative Stress, Inflammatory Phenotype Transformation, and Apoptosis of Human Brain Smooth Muscle Cells Via TGF-β1-NOX4 Pathway Xianjun Tan 1,2,3 & Tao Li 1,3,4 & Shaowei Zhu 1,3 & Weiying Zhong 1,3 & Feng Li 1 & Yunyan Wang 1,3 Received: 10 November 2019 / Accepted: 22 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Secreted protein acidic and rich in cysteine (SPARC) has a close association with inflammatory response and oxidative stress in tissues and is widely expressed in intracranial aneurysms (IAs), especially in smooth muscle cells. Therefore, it is inferred that SPARC might be involved in the formation and development of IAs through the inflammatory response pathway or oxidative stress pathway. The aim of this study is to investigate the pathological mechanism of SPARC in oxidative stress, inflammation, and apoptosis during the formation of IAs, as well as the involvement of TGF-β1 and NOX4 molecules. Human brain vascular smooth muscle cells (HBVSMCs) were selected as experimental objects. After the cells were stimulated by recombinant human SPARC protein in vitro, the ROS level in the cells was measured using an ID/ROS fluorescence analysis kit combined with fluorescence microscope and flow cytometry. The related protein expression in HBVSMCs was measured using western blotting. The mitochondrial membrane potential change was detected using a mitochondrial membrane potential kit and laser confocal microscope. The mechanism was explored by intervention with reactive oxygen scavengers N-acetylcysteine (NAC), TGF-β1 inhibitor (SD-208), and siRNA knockout. The results showed that SPARC upregulated the expression of NOX4 through the TGF-β1-dependent signaling pathway, leading to oxidative stress and pro-inflammatory matrix behavior and apoptosis in HBVSMCs. These findings demonstrated that SPARC may promote the progression of IAs. Keywords SPARC . Intracranial aneurysms . Oxidative stress . Phenotype transformation . TGF-β1-NOX4 pathway . Human brain smooth muscle cells
Introduction Intracranial aneurysms (IAs) are relatively common lesions, leading to catastrophic subarachnoid hemorrhage with high mortality and morbidity rates. The pathological mechanism of formation of IAs is associated with inflammatory cell infiltration, smooth muscle cell apoptosis, and degradation of
* Yunyan Wang [email protected] 1
Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
2
Department of Neurosurgery, People’s Hospital of Chiping City, Liaocheng City, Shandong Province, China
3
Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong Province, China
4
Department of Neurosurgery, the No.4 People’s Hospital of Jinan, Jinan City, Shandong Province, China
extracellular matrix. According to our and others studies, secreted protein acidic and rich in cysteine (SPARC) is widely expressed in human IAs tissues, especially in vascular smooth muscle cells (VSMCs) (Li et al. 2013), and can r
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