title: Nuclear envelope proteins Nesprin2 and LaminA regulate proliferation and apoptosis of vascular endothelial cells in response to shear stress.
abstract: The dysfunction of vascular endothelial cells (ECs) influenced by flow shear stress is crucial for vascular remodeling. However, the roles of nuclear envelope (NE) proteins in shear stress-induced EC dysfunction are still unknown. Our results indicated that, compared with normal shear stress (NSS), low shear stress (LowSS) suppressed the expression of two types of NE proteins, Nesprin2 and LaminA, and increased the proliferation and apoptosis of ECs. Targeted small interfering RNA (siRNA) and gene overexpression plasmid transfection revealed that Nesprin2 and LaminA participate in the regulation of EC proliferation and apoptosis. A protein/DNA array was further used to detect the activation of transcription factors in ECs following transfection with target siRNAs and overexpression plasmids. The regulation of AP-2 and TFIID mediated by Nesprin2 and the activation of Stat-1, Stat-3, Stat-5 and Stat-6 by LaminA were verified under shear stress. Furthermore, using Ingenuity Pathway Analysis software and real-time RT-PCR, the effects of Nesprin2 or LaminA on the downstream target genes of AP-2, TFIID, and Stat-1, Stat-3, Stat-5 and Stat-6, respectively, were investigated under LowSS. Our study has revealed that NE proteins are novel mechano-sensitive molecules in ECs. LowSS suppresses the expression of Nesprin2 and LaminA, which may subsequently modulate the activation of important transcription factors and eventually lead to EC dysfunction.
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Han
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Yao
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Wang
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Bao-Rong
authors.initials: BR
authors.lastname: Shen
authors.affiliation: Department of Bioengineering, University of CA, San Diego, USA.
authors.forename: Binbin
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Department of Bioengineering, University of CA, San Diego, USA.
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zong-Lai
authors.initials: ZL
authors.lastname: Jiang
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. Electronic address: qiyx@sjtu.edu.cn.
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Qi
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D053263:Gene Regulatory Networks; D034904:Lamin Type A / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D033081:Shear Strength; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D034904:Lamin Type A; D009419:Nerve Tissue Proteins; D014157:Transcription Factors
keywords: Dysfunction; Endothelial cells; Nuclear envelope proteins; Shear stress; Transcription factor; Vascular remodeling