Title |
Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester) ester nanovector induces donor-specific liver allograft tolerance
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Published in |
International Journal of Nanomedicine, July 2015
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DOI | 10.2147/ijn.s81413 |
Pubmed ID | |
Authors |
Fanguo Hu, Hanjie Wang, Shuangnan Zhang, Yao Peng, Lin Su, Jin Chang, Gang Liu |
Abstract |
Toll-like receptors (TLRs) activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88), which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester) (HGPAE) nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88 (pMyD88). We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88 expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88 as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 17% |
Unknown | 5 | 83% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 3 | 50% |
Members of the public | 2 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 7 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 1 | 14% |
Researcher | 1 | 14% |
Student > Doctoral Student | 1 | 14% |
Student > Master | 1 | 14% |
Unknown | 3 | 43% |
Readers by discipline | Count | As % |
---|---|---|
Nursing and Health Professions | 1 | 14% |
Chemistry | 1 | 14% |
Medicine and Dentistry | 1 | 14% |
Unknown | 4 | 57% |