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Gene therapy of radiation fibrosis using adenovirus expressing decoy wnt receptor (sLRP6E1E2)
DC Field | Value | Language |
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dc.contributor.author | 이동원 | - |
dc.date.accessioned | 2017-07-11T16:10:27Z | - |
dc.date.available | 2017-07-11T16:10:27Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/149179 | - |
dc.description | Dept. of Medicine/박사 | - |
dc.description.abstract | Progressive fibrosis of the dermal tissues is a challenging complication of radiotherapy, since mechanism of action is not fully understood and there are only few available treatments. The canonical wnt/β-catenin signaling athway plays an important role in fibrotic reaction as well as epithelial-to-mesenchymal transition. We verified whether that inhibition of wnt/β-catenin signaling pathway with sLRP6E1E2 that is binding to extracellular wnt ligands would ameliorate radiation-induced fibrosis both in vitro and in vivo. Radiation with a single dose of 2Gy not only facilitated fibrotic reaction in cultured human dermal fibroblasts via activated wnt/β-catenin pathway, but is also responsible for epithelial to mesenchymal transition of cultured keratinocytes, developing collagen-producing mesenchymal cells. sLRP6E1E2-expressing adenovirus treatment exerted anti-fibrotic actions in irradiated cultured dermal fibroblasts and keratinocytes. In a mouse model, a single fraction of 15Gy was delivered to the dorsal skin of each mouse. Thirty mice were randomized into three groups: PBS, control adenovirus (dE1-k35) and decoy wnt receptor-expressing adenovirus (dE1-k35/sLRP6E1E2). The mice were observed for 16 weeks, and there was no significantly different gross change observed in comparison with controls. In semi-quantitative analysis with Masson’s trichrome staining, excessive collagen deposition was suppressed by sLRP6E1E2-expressing adenovirus treatment. These results support that modulation of wnt/β-catenin pathway has the potential to decrease the severity of radiation-induced dermal fibrosis. | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Gene therapy of radiation fibrosis using adenovirus expressing decoy wnt receptor (sLRP6E1E2) | - |
dc.title.alternative | Wnt를 억제하는 sLRP6E1E2 발현 아데노바이러스를 이용한 방사선 섬유화에 대한 유전자 치료 | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Lee, Dong Won | - |
dc.type.local | Dissertation | - |
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