Mechanical stretch enhances the expression of resistin gene in cultured cardiomyocytes via tumor necrosis factor-alpha.
The heart is a resistin target tissue and can function as an autocrine organ. We sought to investigate whether cyclic mechanical stretch could induce resistin expression in cardiomyocytes and to test whether there is a link between the stretch-induced TNF-alpha and resistin. Neonatal Wistar rat cardiomyocytes grown on a flexible membrane base were stretched by vacuum to 20% of maximum elongation at 60 cycles/min. Cyclic stretch significantly increased resistin protein and mRNA expression after 2-18 h of stretch. Addition of PD-98059, TNF-alpha antibody, TNF-alpha receptor antibody, and ERK MAP kinase small interfering RNA 30 min before stretch inhibited the induction of resistin protein. Cyclic stretch increased, whereas PD-98059 abolished, the phosphorylated ERK protein. Gel-shift assay showed a significant increase in DNA-protein binding activity of NF-kappaB after stretch, and PD-98059 abolished the DNA-protein binding activity induced by cyclic stretch. DNA binding complexes induced by cyclic stretch could be supershifted by p65 monoclonal antibody. Cyclic stretch increased resistin promoter activity, whereas PD-98059 and p65 antibody decreased resistin promoter activity. Cyclic stretch significantly increased TNF-alpha secretion from myocytes. Recombinant resistin protein and conditioned medium from stretched cardiomyocytes reduced glucose uptake in cardiomyocytes, and recombinant small interfering RNA of resistin or TNF-alpha antibody reversed glucose uptake. In conclusion, cyclic mechanical stretch enhances resistin expression in cultured rat neonatal cardiomyocytes. The stretch-induced resistin is mediated by TNF-alpha, at least in part, through ERK MAP kinase and NF-kappaB pathways. Glucose uptake in cardiomyocytes was reduced by resistin upregulation.
Wang
Bao-Wei
BW
Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Hung
Huei-Fong
HF
Chang
Hang
H
Kuan
Peiliang
P
Shyu
Kou-Gi
KG
D000818:Animals; D000831:Animals, Newborn; D001166:Arteriovenous Shunt, Surgical; D048430:Cell Shape; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D008465:Mechanoreceptors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000235:genetics; D023421:Models, Animal; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D052243:Resistin / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D005419:Flavonoids; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D052243:Resistin; C499622:Retn protein, rat; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one