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dc.description.abstractTranscriptional coactivator with PDZ-binding motif (TAZ) functions as a critical regulator for mesenchymal stem cells differentiation into osteoblasts and adipocytes. Since TAZ-deficient mice develop emphysema and glomerulocystic kidney disease, TAZ may have roles in the lung and kidney. In this study, TAZ functions in the lung were investigated using TAZ knockout (KO) mice. TAZ-deficient lung reveals severe pulmonary fibrosis in a proportion to ageing and expressed diminished levels of lung epithelial cell markers such as surfactant protein C, clara cell secretory protein, and Vascular Endothelial growth factor, which were main characteristics in hyperoxia-injured lung. Interestingly, TAZ expression decreased by hyperoxic conditions and epithelial cell markers were further reduced in hyperoxia-stimulated TAZ KO mice. It is recently reported that hyperoxia-induced signaling molecules increased sulfonylation of peroxiredoxin and expression of sulfiredoxin depending on Nuclear factor erythroid 2-related factor 2. Notably, TAZ deficiency upregulated expression of sulfiredoxin and sulfonylated peroxiredoxin in the lung without hyperoxic stimulation. Suggesting a suppressive activity of TAZ on the expression of oxidative stress-induced signaling molecules. These results suggest that TAZ may control the expression of signaling molecules in response to oxidative stress and modulate lung homeostasis under normoxic condition.;Transcriptional coactivator with PDZ-binding motif (TAZ)는 조골세포와 지방세포로의 성체 줄기세포의 분화를 조절하는데 있어서 중요한 역할을 한다고 알려져 있다. TAZ가 결핍된 mice에서 emphysema와 glomerulocystic kidney disease가 일어난다는 것은 이미 보고 되어진 바 있으며, 이로서 TAZ가 lung과 kidney의 기능에 중요한 역할을 한다고 생각할 수 있다. 이 논문에서는 TAZ가 결핍된 mice를 이용하여 lung에서의 TAZ의 기능을 연구하고자 하였다. TAZ가 결핍된 mice는 lung에서 심각한 pulmonary fibrosis 을 보였으며, 이것은 나이가 들수록 심해지는 경향을 보였다. 또한 TAZ가 결핍된 mice의 lung 에서 WT mice보다 lung epithelial cell marker인 surfactant protein C, vascular endothelial growth factor, clara cell secretory protein등이 감소되어 있음이 증명되었다. 이 marker들은 hyperoxia에 의한 lung damage의 발생시에 감소되는 것으로 알려져 있는 것들로서, 더불어 hyperoxia shock을 받은 폐조직에서 TAZ의 level이 감소 되어 있음을 확인하였다. 즉, hyperoxia로 인한 lung damage와 TAZ의 결핍으로 인해 일어나는 lung damage 사이에 유사한 병리학적 특징이 관찰됨을 확인하였다. 추가적으로, 보고된 hyperoxia 유발 폐조직에서의 sulfonylated peroxiredoxin 증가와, Nuclear factor erythroid 2-related factor 2 의존적 sulfiredoxin 증가가 TAZ 결핍 폐 조직에서도 유의성 있게 일어나고 있음을 확인하였다. 결론적으로 TAZ가 oxidative stress 신호 전달에 관여하는 sulfonylated peroxiredoxin과 sulfiredoxin 유전자 발현을 시킬 수 있음을 의미하며, oxidative stress에 대항한 폐 조직에서의 기능 항상성 조절에 TAZ의 중요성을 제시하였다.-
dc.description.tableofcontents1. Introduction 1 2. Material and Method 4 2.1. Animal 4 2.1.1. Mice 4 2.1.2. PCR for genotyping 4 2.2. Histology 5 2.2.1. Lung preparing for staining 5 2.2.2. Hematoxylin and eosin staining 6 2.2.3. Masson trichrome staining 6 2.3. Cell culture 7 2.3.1. Cells and cell culture conditions 7 2.3.2. CFSE staining 8 2.4. Analysis of protein and mRNA 8 2.4.1. Real-time PCR analysis 8 2.4.2. Western blotting 9 3. Result 12 3.1. Fibrosis in TAZ KO mice lung 12 3.1.1. TAZ KO mice lung has shown fibrosis 12 3.1.2. Reduction of lung fibrosis marker proteins in TAZ KO mice 17 3.2. Expose hyperoxia mice lung has shown fibrosis 21 3.2.1. Hyperoxia-induced fibrosis model 21 3.2.2. Exposed hyperoxia mice lung reduction of TAZ expression level 25 3.3. Hyperoxia-induced fibrosis and TAZ KO-induced fibrosis caused decreased proliferation 30 3.4. Effect of oxidative stress in TAZ KO mice 39 4. Discussion 42 References 46 국문 초록 54 Acknowledgements 56-
dc.format.extent3578560 bytes-
dc.publisher이화여자대학교 대학원-
dc.titleSevere oxygen induced lung damage by TAZ deficiency-
dc.typeMaster's Thesis-
dc.format.pagexi, 58 p.-
dc.identifier.major대학원 생명·약학부약학전공- 2-
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