Endotel hücrenin farklı diyabet stresleri altında mononükleer hücreleri bağlama ve koruyucu genleri ifadeleme yanıtları
Küçük Resim Yok
Tarih
2016
Yazarlar
Dergi Başlığı
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Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
ÖZET Tez çalışmamızda endotel hücrelerin farklı diyabet streslerine özgül yanıtlarında literatürde henüz aydınlatılmamış iki noktaya odaklanılmıştır. Bu noktalar hangi diyabet stresinin endotel hücreyi hangi lökosit kombinasyonunda infiltrasyona iteklediği ve hangi koruyucu gen ifadesine sürüklendiğidir. Bu çalışmada olarak adezyon testi ile monosit ve T lenfosit hücrelerin glomerüler endotel tabakalara in vitro yapışma profili ve RT-PZR yöntemiyle A1'ler, A20, HO-1 koruyucu gen mRNA'larının endotel hücrelerde ifade profili karşılaştırılmalı olarak incelenmiştir. Elde edilen bulgulara göre; (1) endotel hücrelere monositlerin Tip I DM modelinde sırasıyla Tip II DM ve IGT modellerine göre 0,5 ve 0,8 kat, T lenfositlerin ise sırasıyla Tip II DM ve IGT modellerine göre 0,4 ve 0,5 kat daha az yapıştığı; A1'ler/ A20/ HO-1 mRNA'larının hücrelerde sırasıyla 2,4/ 22/ 74 kat fazla ifade edildiği; (2) monositlerin Tip II DM modelinde Tip I DM modeline göre 1,8 kat, IGT modeline göre ise 1,1 kat, T lenfositlerin Tip I DM modeline göre 2 kat, IGT modeline ise göre 1,5 kat daha fazla yapıştığı; aynı mRNA'ların hücrelerde sırasıyla 1,4/ 8/ 103 kat fazla ifade edildiği; (3) monositlerin IGT modelinde Tip I DM modeline göre 1,1 kat fazla, Tip II DM modeline göre 0,6 kat az yapıştığı, T lenfositlerin IGT modelinde Tip I DM modeline göre 1,9 kat fazla, Tip II DM modeline göre ise 0,9 kat az yapıştığı; aynı mRNA'ların hücrelerde sırasıyla 0,7/ 22/ 169 kat fazla ifade edildiği bulunmuştur. Koruyucu gen ifade yanıtının glomerüler hücrelerde tek ve aortik hücrelerde iki fazlı geliştiği belirlenmiştir. Elde edilen bulgular değişik tipte diyabet stresinin mononükleer hücre adezyon ve adaptif yanıtını endotel hücrelerde nasıl farklı uyardığını göstermiştir. Özellikle glomerüler lezyon gelişimini engelleyici ve modifiye edici farmakoterapötiklerin geliştirilmesi düşünüldüğünde hangi lökosit ve koruyucu genin hangi diyabet tipinde öncelikli hedeflenmesi gerektiği ortaya konmuş, antagomir drug tasarımında hedeflenebilecek olası miRNA'lar saptanmıştır. Anahtar kelimeler: endotel hücre, diyabet, koruyucu gen
MONONUCLEAR CELL BINDING AND PROTECTIVE GENE EXPRESSION RESPONSES OF THE ENDOTHELIAL CELLS UNDER DIFFERENT DIABETES STRESSES SUMMARY In this dissertation stress specific responses of the varied diabetes stresses in endothelial cells were studied by focusing two points which had not been lightened yet in literature. These points are, which diabetes stress push endothelial cells which type of inflitrative leukocyte combination, and which type of protective gene expression. In the study, in vitro adhesion profiles of the monocytes and T lymphocytes on the aortic and glomerular endothelial cell layers, which were activated by varied types of diabetes stress, and, mRNA expression profiles of the A1s, A20, HO-1 protective genes again in the same endothelial cells under similar activation conditions have been identified. According to the findings obtained; (1) in type I DM model, monocytes adhere to the endothelial cells 0,5 and 0,8 times less compared to type II and IGT models respectively; while T lymphocytes adhere 0,5 and 0,8 times less compared to type II and IGT models respectively, A1s/ A20/ HO-1 mRNAs are expressed 2,4/ 22/ 74 times more in cells respectively; (2) monocytes adhere 1,8 times more in type 2 DM model compared to type I DM model, and 1,5 times more compared to IGT model; the same mRNAs are expressed 1,4/ 8/ 103 times more in cells respectively, the same mRNAs are expressed 1,4/ 8/ 103 times more (3) monocytes adhere 1,1 times more in IGT model compared to type I DM model, and 0,6 times less compared to type II DM model, while T lymphocytes adhere 1,9 times more in IGT model compared to type 1 model, and 0,9 times less compared to type II DM model; the same mRNAs are expressed 0,7/ 22/ 169 times more in cells respectively. The results revealed that which molecules in which ratio should be targeted for inhibition of varied pathological process in endothelial cells in response to varied diabetes stress, and modifying the adaptif response. These results will enlighten the adjustments of drug combinations when concerned about development of relevant pharmacotherapeutics. Key words: endothelial cells, diabetes, protective genes.
MONONUCLEAR CELL BINDING AND PROTECTIVE GENE EXPRESSION RESPONSES OF THE ENDOTHELIAL CELLS UNDER DIFFERENT DIABETES STRESSES SUMMARY In this dissertation stress specific responses of the varied diabetes stresses in endothelial cells were studied by focusing two points which had not been lightened yet in literature. These points are, which diabetes stress push endothelial cells which type of inflitrative leukocyte combination, and which type of protective gene expression. In the study, in vitro adhesion profiles of the monocytes and T lymphocytes on the aortic and glomerular endothelial cell layers, which were activated by varied types of diabetes stress, and, mRNA expression profiles of the A1s, A20, HO-1 protective genes again in the same endothelial cells under similar activation conditions have been identified. According to the findings obtained; (1) in type I DM model, monocytes adhere to the endothelial cells 0,5 and 0,8 times less compared to type II and IGT models respectively; while T lymphocytes adhere 0,5 and 0,8 times less compared to type II and IGT models respectively, A1s/ A20/ HO-1 mRNAs are expressed 2,4/ 22/ 74 times more in cells respectively; (2) monocytes adhere 1,8 times more in type 2 DM model compared to type I DM model, and 1,5 times more compared to IGT model; the same mRNAs are expressed 1,4/ 8/ 103 times more in cells respectively, the same mRNAs are expressed 1,4/ 8/ 103 times more (3) monocytes adhere 1,1 times more in IGT model compared to type I DM model, and 0,6 times less compared to type II DM model, while T lymphocytes adhere 1,9 times more in IGT model compared to type 1 model, and 0,9 times less compared to type II DM model; the same mRNAs are expressed 0,7/ 22/ 169 times more in cells respectively. The results revealed that which molecules in which ratio should be targeted for inhibition of varied pathological process in endothelial cells in response to varied diabetes stress, and modifying the adaptif response. These results will enlighten the adjustments of drug combinations when concerned about development of relevant pharmacotherapeutics. Key words: endothelial cells, diabetes, protective genes.
Açıklama
Doktora
Anahtar Kelimeler
Moleküler Tıp, Molecular Medicine
