کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5434023 1509004 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
HMGB1 modulation in pancreatic islets using a cell-permeable A-box fragment
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
HMGB1 modulation in pancreatic islets using a cell-permeable A-box fragment
چکیده انگلیسی

Although pancreatic islet implantation is an attractive strategy for curing diabetes mellitus, implanted cells are immunologically eliminated due to early islet graft loss. One of main issues in early islet graft loss is the secretion of high-mobility group-box-1 (HMGB1) protein from the damaged islet cells, which is known as a cytokine-like factor. Therefore, regulating the activity of HMGB1 protein offers an alternative strategy for improving outcomes of islet cell therapy. To this end, we first demonstrated that HMGB1 protein could be bound to its A-box fragment (HMGB1 A-box) with higher binding affinity, resembling anti-HMGB1 antibody. To be used as a pharmaceutical protein ex vivo, TAT-labeled HMGB1 A-box-His6 (TAT-HMGB1A) was structurally modified for cellular membrane penetration. TAT-HMGB1A significantly reduced secretion of endogenous HMGB1 protein through interaction in the cytosol without any damage to the viability or functionality of the islets. When TAT-HMGB1A-treated islets were implanted into diabetic nude mice, they completely cured diabetes, as evidenced by stable blood glucose level. TAT-HMGB1A treatment could also reduce the marginal islet mass needed to cure diabetes. Furthermore, TAT-HMGB1A positively protected xenotransplanted islets from xenogeneic immune reactions. Collectively, cell-penetrable TAT-HMGB1A could be used to modulate HMGB1 activity to increase successful outcomes of ex vivo pancreatic islet cell therapy.

Ex vivo cell-permeable HMGB1 A-box fragment delivery into pancreatic islet could offer enhanced viability of islets from immune reactions, thereby supporting successful pancreatic islet transplantation to cure diabetes mellitus.195

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 246, 28 January 2017, Pages 155-163
نویسندگان
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