title: Actin cytoskeleton-dependent pathways for ADMA-induced NF-κB activation and TGF-β high expression in human renal glomerular endothelial cells.
abstract: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is considered to be an independent risk factor in the progression of chronic kidney diseases (CKD). It can induce kidney fibrosis by increasing transforming growth factor (TGF)-β1 expression, but its molecular mechanism is unclear. The aim of the present study was to investigate the role of actin cytoskeleton in ADMA-induced TGF-β1 high expression in human renal glomerular endothelial cells (HRGECs). The structure of stress fibers was visualized by immunofluorescence, nuclear factor-κB (NF-κB) DNA-binding activity was assessed by an electrophoretic mobility shift assay and TGF-β1 expression was assessed by western blot analysis. Results showed that ADMA induced the assembly of stress fibers, DNA binding of NF-κB, and increasing expression of TGF-β1. When the dynamics of actin cytoskeleton was perturbed by the actin-depolymerizing agent cytochalasin D and the actin-stabilizing agent jasplakinolide, or ablation of stress fiber bundles by the nicotineamide adenine dinucleotide phosphate oxidase inhibitor apocynin and p38 mitogen-activated protein kinase inhibitor SB203580, ADMA-induced DNA binding of NF-κB and TGF-β1 expression were inhibited. These results revealed an actin cytoskeleton-dependent mechanism in ADMA-induced NF-κB activation and TGF-β1 high expression in HRGECs. The specific targeting of the actin cytoskeleton may be a useful strategy to prevent ADMA-activated kidney fibrosis in CKD.
authors.affiliation: Department of Nephrology,  Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing 100050,  China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Wang
authors.forename: Dongliang
authors.initials: D
authors.lastname: Zhang
authors.forename: Junfang
authors.initials: J
authors.lastname: Zheng
authors.forename: Yiduo
authors.initials: Y
authors.lastname: Feng
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenhu
authors.initials: W
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000199:Actins; D017931:DNA Primers; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; C018524:N,N-dimethylarginine; D001120:Arginine