A macrophage-specific synthetic promoter for therapeutic application of adiponectin View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-04

AUTHORS

W S Kang, J S Kwon, H B Kim, H-Y Jeong, H J Kang, M H Jeong, J G Cho, J C Park, Y S Kim, Y Ahn

ABSTRACT

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. More... »

PAGES

353

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gt.2014.3

DOI

http://dx.doi.org/10.1038/gt.2014.3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052562543

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24500526


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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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