Influence of Endothelial Cells on Vascular Smooth Muscle Cells Phenotype after Irradiation

作者: Fabien Milliat , Agnès François , Muriel Isoir , Eric Deutsch , Radia Tamarat

DOI: 10.2353/AJPATH.2006.060116

关键词: Immediate early proteinInternal medicineCell biologyEndothelial stem cellBiologyMyocyteGrowth factorTransforming growth factorEndocrinologyVascular smooth muscleEndotheliumTransforming growth factor beta

摘要: Damage to vessels is one of the most common effects therapeutic irradiation on normal tissues. We undertook a study in patients treated with preoperative radiotherapy and demonstrated vivo importance proliferation, migration, fibrogenic phenotype vascular smooth muscle cells (VSMCs) radiation-induced damage. These lesions may result from imbalance cross talk between endothelial (ECs) VSMCs. Using co-culture models, we examined whether ECs influence In presence irradiated ECs, proliferation migration VSMCs were increased. Moreover, expressions alpha-smooth actin, connective tissue growth factor, plasminogen activator inhibitor type 1, heat shock protein 27, collagen III, alpha 1 up-regulated exposed ECs. Secretion transforming factor (TGF)-beta1 was increased after activated Smad pathway by inducing Smad3/4 nuclear translocation Smad-dependent promoter activation. small interferring RNA targeting Smad3 TGFbeta-RII neutralizing antibody, demonstrate that TGF-beta1/TGF-beta-RII/Smad3 involved induced conclusion, show patients. vitro these fundamental mechanisms damages.

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