RRC ID 49214
Author Shinohara M, Sumino Y, Sato F, Kiyono T, Hashimoto N, Mimata H.
Title Tumor necrosis factor-alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter.
Journal Int J Urol
Abstract OBJECTIVES:To examine the inhibitory effects of tumor necrosis factor-α on myogenic differentiation of human urethral rhabdosphincter cells.
METHODS:A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin-dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human rhabdosphincter cells were induced for myogenic differentiation with recombinant human tumor necrosis factor-α and/or the tumor necrosis factor-α antagonist etanercept at different concentrations, and activation of signaling pathways was monitored.
RESULTS:Human rhabdosphincter cells were selectively cultured for at least 40 passages. Molecular analysis confirmed the expression of myosin heavy chain, which is a specific marker of differentiated muscle cells, significantly increased after differentiation induction. Although tumor necrosis factor-α treatment reduced the myosin heavy chain expression in a concentration-dependent manner, etanercept inhibited this suppression. Tumor necrosis factor-α suppressed phosphorylation of protein kinase B and p38, whereas etanercept pretreatment promoted phosphorylation and myosin heavy chain expression in a concentration-dependent manner.
CONCLUSIONS:Tumor necrosis factor-α inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Inhibition of tumor necrosis factor-α might be a useful strategy to treat stress urinary incontinence.
Volume 24(6)
Pages 461-467
Published 2017-6-1
DOI 10.1111/iju.13330
PMID 28332237
MeSH Cell Differentiation / drug effects Cell Differentiation / physiology* Cells, Cultured Cystectomy Etanercept / pharmacology Etanercept / therapeutic use Humans MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* Male Middle Aged Muscle Development / drug effects Muscle Development / physiology Muscle, Skeletal / cytology Myoblasts, Skeletal / drug effects Myoblasts, Skeletal / physiology* Myosin Heavy Chains / metabolism Phosphatidylinositol 3-Kinases / metabolism Phosphorylation / drug effects Primary Cell Culture Recombinant Proteins / isolation & purification Recombinant Proteins / metabolism Tumor Necrosis Factor-alpha / antagonists & inhibitors Tumor Necrosis Factor-alpha / isolation & purification Tumor Necrosis Factor-alpha / physiology* Urethra / cytology Urethra / drug effects Urethra / physiology Urinary Bladder Neoplasms / surgery Urinary Incontinence, Stress / drug therapy Urinary Incontinence, Stress / physiopathology
IF 2.445
Times Cited 2
DNA material CSII-CMV-RfA (RDB04386)