Kowalewski Radoslaw, Malkowski Andrzej, Gacko Marek, Sobolewski Krzysztof
Department of Vascular Surgery and Transplantology, Medical University of Bialystok, Poland.
Folia Histochem Cytobiol. 2010 Dec;48(4):542-8. doi: 10.2478/v10042-010-0041-z.
Extensive extracellular matrix remodeling of the vein wall is involved in varicose veins pathogenesis. This process is controlled by numerous factors, including peptide growth factors. The aim of the study was to evaluate influence of thrombophlebitis on TGF-β1 and its signaling pathway in the vein wall. TGF-β1 mRNAlevels, growth factor content and its expression were evaluated by RT-PCR, ELISA, and western blot methods, respectively, in the walls of normal veins, varicose veins and varicose veins complicated by thrombophlebitis. Western blot analysis was used to assess TGF-β receptor type II (TGF-β RII) and p-Smad2/3 protein expression in the investigated material. Unchanged mRNA levels of TGF-β1, decreased TGF-β1 content, as well as decreased expression of latent and active forms of TGF-β1 were found in varicose veins. Increased expression of TGF-β RII and p-Smad2/3 were found in varicose veins. Thrombophlebitis led to increased protein expression of the TGF-β1 active form and p-Smad2/3 in the vein wall compared to varicose veins. TGF-β1 may play a role in the disease pathogenesis because of increased expression and activation of its receptor in the wall of varicose veins. Thrombophlebitis accelerates activation of TGF-β1 and activity of its receptor in the varicose vein wall.
静脉壁广泛的细胞外基质重塑参与了静脉曲张的发病机制。这一过程受多种因素控制，包括肽生长因子。本研究的目的是评估血栓性静脉炎对静脉壁中转化生长因子-β1（TGF-β1）及其信号通路的影响。分别采用逆转录-聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）和蛋白质免疫印迹法，对正常静脉壁、静脉曲张壁以及并发血栓性静脉炎的静脉曲张壁中的TGF-β1信使核糖核酸（mRNA）水平、生长因子含量及其表达进行评估。采用蛋白质免疫印迹分析评估所研究材料中II型TGF-β受体（TGF-β RII）和磷酸化Smad2/3蛋白的表达。在静脉曲张中发现TGF-β1的mRNA水平未改变、TGF-β1含量降低，以及TGF-β1的潜伏形式和活性形式的表达均降低。在静脉曲张中发现TGF-β RII和磷酸化Smad2/3的表达增加。与静脉曲张相比，血栓性静脉炎导致静脉壁中TGF-β1活性形式和磷酸化Smad2/3的蛋白表达增加。由于TGF-β1在静脉曲张壁中的受体表达增加和激活，其可能在疾病发病机制中发挥作用。血栓性静脉炎加速了静脉曲张壁中TGF-β1的激活及其受体的活性。
