V. B. ÇETİNTAŞ, F OLTULU, B KOSOVA, A. YAVAŞOĞLU, E OYTUN, H. AKTUĞ

Endotelin tip-A reseptör antagonist tedavisinin diyabetik sıçan aortunda hücresel bağlantıların ve hücre adezyon moleküllerinin gen ekspresyonlarına etkileri

Amaç: Bu çalışmada, tedavi amaçlı uygulanan endotelin reseptör antagonist-A’nın (ERA-A) streptozotozin (STZ) ile indüklenmiş diyabetik sıçanların aortlarındaki hücresel bağlantı ve hücre adezyon moleküllerinin gen ekspresyonları üzerine etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Toplamda 80 sıçan 4 eşit gruba bölünerek incelenmiştir: Grup1: Kontrol, Grup2: ERA-A uygulanan, Grup3: Diyabet ve Grup4: Diyabet sonrası ERA-A uygulanan grup. Kırk sıçanda tek doz STZ enjeksiyonu ile diyabet indüklenmiştir ve hayvanlar 2 ay takip edilmiştir. Ayrıca, 20 diyabetik ve 20 sağlıklı sıçana 7. ve 15. günlerde ERA-A uygulanmıştır. Sıçan aort doku örneklerindeki hücreler arası bağlantı birimlerinin bileşenlerini ve hücre adezyon moleküllerini kodlayan genlerin ekspresyonları kantitatif gerçek-zamanlı ters transkripsiyon-polimer zincir reaksiyonu ile analiz edilmiştir. Bulgular: Konneksin-30 (Cx30), Cx33, Cx37, Cx40 ve Cx45 ekspresyonları diyabet grubunda azalmıştır. ERA-A uygulanan diyabetik sıçanlarda ise Cx33 ve Cx36 ekspresyonları istatistiksel olarak anlamlı artış göstermiştir. Diyabet grubu kontrol grubu ile karşılaştırıldığında α-1-katenin ekspresyonunun anlamlı olarak arttığı, ve β-1-katenin ekspresyonunun da anlamlı olarak azaldığı görülmüştür. Sonuç: Çalışmamızda, endotel hücrelerin hücreler arası iletişimini sağlayan oluklu bağlantılarında diyabet ile indüklenen hasar saptanmıştır. ERA-A uygulaması bazı konneksin alt tiplerinin ekspresyonlarını arttırdığı için, bu durumun sağaltımı için gelecekteki rutin kullanımı düşünülebilir.

Effects of endothelin type-A receptor antagonist therapy on gene expressions of cell junctions and cell adhesion molecules in diabetic rat aorta

Aim: The aim of this study was to investigate the effects of endothelin receptor type-A antagonist (ERA-A), that has been applied for therapeutic reasons, on the gene expressions of cell junctions and cell adhesion molecules in the aorta of streptozotocin (STZ) induced diabetic rats. Materials and Methods: A total of 80 rats were analyzed in 4 equally distributed groups: Group 1: Control, Group 2: ERA-A administered, Group 3: Diabetic, and Group 4: Diabetic ERA-A treated. Diabetes was induced in 40 rats by a single injection of STZ and the animals were followed for 2 months. Twenty diabetic and 20 healthy rats were also treated with ERA-A at days 7 and 15. The expressions of genes coding for cell junctions and cell adhesion molecules in rat aortic tissue samples were analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Results: The expressions of connexin-30 (Cx30), Cx33, Cx37, Cx40, and Cx45 were decreased in the diabetic group. A statistically significant increase in the expressions of Cx33 and Cx36 was determined in diabetic rats treated with ERA-A. When the diabetic group was compared to the control group a significant increase in the expression of α- 1-catenin, and a significant decrease in the expression of β-1-catenin was found. Conclusion: In our study, diabetes induced damages in the intercellular communication of endothelial cells provided by gap junctions. Since administration of ERA-A has led to an increase in the expression of some connexin subtypes, its routine use in the treatment of this condition could be considered in the future.

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