자주쓰는 링크
작성일 : 14-09-21 12:28
| 연구단계 | 1단계 :1년차 | ||
| 논문제목(영문) | A macrophage-specific synthetic promoter for therapeutic application of adiponectin. | ||
| 국내외구분 | 국외 | SCI여부 | SCI |
| 연구책임자역활 | 교신저자 | 논문기여율 | 30% |
| 주저자명 | Kang WS | ||
| 교신저자명 | Ahn Y | ||
| 공동저자명 | Kwon JS, Kim HB, Jeong HY, Kang HJ, Jeong MH, Cho JG, Park JC, Kim YS | ||
| 게제년월일 | 2014-04-01 | ||
| ISSN | 0969-7128 | ||
| Impact Factor | 4.196 | ||
| 학술지명 | GENE THER | ||
| 서지사항 | 0집 / 21권 / 4호, 페이지(353 - 362) | ||
| 병기표기 | 단독 | ||
| Acknowledgement 기재여부 |
예
※ Acknowledgement가 기재된 논문만 연구과제의 성과로 인정. - 국문 표기 : "본 연구는 보건복지부 보건의료연구개발사업의 지원에 의하여 이루어진 것임. (HI13C1527)" - 영문 표기 : "This study was supported by a grant of the Korean Health Technology R&D Project, (HI13C1527) Ministry of Health & Welfare, Republic of Korea. " |
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| 요약초록문 (Abstract) 입력 |
Foam cell formation from macrophage is a major cause of atherosclerosis. An efficient macrophage-specific promoter is required for the targeting to macrophages. In this study, we develop a macrophage-specific synthetic promoter for the therapeutic application of adiponectin (APN), an antiatherogenic gene. Synthetic promoter-146 (SP146), registered on the NCBI website (http://www.ncbi.nlm.nih.gov/nuccore/DQ107383), was tested for promoter activities in two non-macrophage cell lines (293 T, HeLa) and a macrophage cell line (RAW264.7, bone marrow-derived macrophages). To enforce macrophage specificity, partial elements of p47(phox) including the PU.1 site with various lengths (-C1, -C2 and -C3) were inserted next to the synthetic promoters. SP146-C1 showed the highest specificity and efficacy in RAW264.7 cells and was selected for development of an APN-carrying macrophage-specific promoter. Green fluorescent protein (GFP)- or APN-expressing lentivirus under SP146-C1 (Lenti-SP-GFP or Lenti-SP-APN, respectively) showed the highest expression efficacy in RAW264.7 cells compared with the non-macrophage cell lines. APN overexpression in RAW264.7 cells successfully inhibited intracellular lipid accumulation, and atherosclerotic lesions and lipid accumulation were significantly reduced by Lenti-SP-APN in ApoE-/- atherosclerosis mice. In conclusion, the synthetic promoter SP146-C1, combined with a p47(phox) promoter element, was successfully developed to target macrophage, and macrophage-specific introduction of APN under SP146-C1 was shown to ameliorate the atherosclerotic pathology. |
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