Tez özetleri Astronomi ve Uzay Bilimleri Anabilim Dalı 2

a Role of Lysyl Oxıdase Inhıbıtıon on Extracellular Matrıx Remodelıng ın the Mıce Lung wıth Fıbrosıs
Pulmonary fibrosis is characterized by an increase in the number of fibroblasts/myofibroblasts and an excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin. The members of lysyl oxidase (LOX) enzyme family regulate the accumulation of collagen fibers in ECM, by catalyzing cross-links bounds among these fibers. An increase in the activity of these enzymes results in pulmonary fibrosis. Tetrathiomolybdate (TM) reduces the LOX activity via its copper-binding characteristic. The current study showed the effects of TM-induced LOX inhibition on the expression of LOX, LOX-like proteins (LOXL-1 and 2), matrix digestion enzymes such as a gelatinase/collagenase (MMP-2/MMP-8) and TIMP-1, a collaganase inhibitory protein, and also evaluated the TM-depended anti-fibrotic effect on pulmonary fibrosis.
In the current study, pulmonary fibrosis was induced by bleomycine instillation via trachea in mice. Adult mice were divided into 4 groups: mice dissected after 21^st days of the first bleomycine (0,8 mg/kg) treatment (I) and their controls (II), mice treated with TM for one week (1.2 mg/day/mice for the first 4 days and 0.9 mg/day/mice for the following 3 days) after 14 days of the first bleomycine instillation and dissected in the 21^st days of experiment (III) and their controls (IV). Mice in groups III and IV fed lower copper diet (2 mg/kg) during the last 7 days of the experiment. Fibrosis score in lung was determined under microscope. Also, the expression of collagen-I, LOX, LOXL-1, LOXL-2, TIMP-1, MMP-2 and MMP-8 proteins were analyzed by Western blotting in lung homogenates.
Bleomycin treatments resulted in expanded pulmonary fibrosis with moderate-severe degree in the mice lung. Mice lung with fibrosis were characterized by an increase in protein levels of collagen-I, activated LOX, LOXL-1, LOXL-2, MMP-2, MMP-8 and TIMP-1, in addition to an excessive accumulation of collagen fibers. In fibrotic mice lung, TM and lower copper diet treatments significantly regressed structural and biochemical alterations, and reduced collagen-I protein expression and collagen accumulation in ECM. In conclusion, TM and lower copper diet treatments may safely be used for regression of pulmonary fibrosis.
  

AĞAY Zaven

Danışman : Doç. Dr. Ayten ERDEM

Anabilim Dalı : Biyoloji

Programı : Temel ve Endüstriyel Mikrobiyoloji

Mezuniyet Yılı : 2014

Tez Savunma Jürisi : Doç Dr. Ayten ERDEM

Prof. Dr. Ayşın ÇOTUK

Doç. Dr. Esra İLHAN SUNGUR

Doç. Dr. İrfan TÜRETGEN

Doç. Dr. Ümran SOYOĞUL GÜRER