Alexandra L. G. Mahoney, Sergio Joshua, N. Nassif, A. Simpson
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引用次数: 0
Abstract
Type 1 Diabetes (T1D) is a chronic metabolic disorder for which current treatments are unable to prevent the onset of complications. Previously, we used an adeno-associated viral vector (AAV8) to deliver furin-cleavable human insulin (INS-FUR) to the livers of diabetic non-obese diabetic (NOD) mice to reverse T1D. The use of the traditional AAV8-INS-FUR vector could not bring about normoglycemia. However, this vector, coupled with a transposon system in the AAV8/piggyBac-INS-FUR vector, was able to do so. This study aimed to investigate the transcriptomic profiles of the livers of diabetic, AAV8-INS-FUR-transduced, and AAV8/piggyBac-INS-FUR-transduced NOD mice and compare these to the normal liver to identify genetic differences resulting from delivery of the AAV8/piggyBac-INS-FUR vector which produced normoglycemia. Differential gene expression was determined by RNA-Seq analysis and differentially expressed genes from each treatment were mapped onto cellular pathways to determine the treatments’ cell signaling and downstream effects. We observed distinct differences between the piggyBac-transduced and diabetic models, particularly in terms of metabolic function and the upregulation of key pancreatic markers in the liver of piggyBac-transduced animals. The success of the AAV8/piggyBac-INS-FUR vector in achieving normoglycemia through stable transduction was evident. However, further engineering is necessary to achieve complete pancreatic transdifferentiation of liver cells.
期刊介绍:
Journal of International Translational Medicine (JITM, ISSN 2227-6394), founded in 2012, is an English academic journal published by Journal of International Translational Medicine Co., Ltd and sponsored by International Fderation of Translational Medicine. JITM is an open access journal freely serving to submit, review, publish, read and download full text and quote. JITM is a quarterly publication with the first issue published in March, 2013, and all articles published in English are compiled and edited by professional graphic designers according to the international compiling and editing standard. All members of the JITM Editorial Board are the famous international specialists in the field of translational medicine who come from twenty different countries and areas such as USA, Britain, France, Germany and so on.