Hydrodynamics-based Transfection of Pancreatic Duodenal Homeobox 1 DNA Improves Hyperglycemia and is Associated with Limited Complications in Diabetic Mice

作者：Chen Tsung Hsing; Yeh Chau Ting; Ho Yu Pin; Hsu Chen Ming; Huang Chau Chun; Shiau Shuen Shian; Liang Chun Kai; Chang Ming Ling^*

来源：Endocrine Journal, 2009, 56(6): 783-790.

DOI：10.1507/endocrj.k09e-112

• Hydrodynamics-based transfection (HBT)
• Pancreatic duodenal homeobox 1 (Pdx1)
• Streptozocin
• Diabetic
• Hepatic inflammation

The biohazards caused by the viral delivery of pancreatic duodenal homeobox gene 1 (Pdx1) to the murine liver limits its application. We aimed to evaluate the feasibility of hydrodynamics-based transfection (HBT) with Pdx1 in improving hyperglycemia. Murine hepatocellular carcinoma (Hepal-6) cells were transfected with the Pdx1-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Pdx1. Hepatic delivery of pcDNA-Pdx1 or pcDNA in streptozocin- induced diabetic mice was achieved by HBT. The sequential serum glucose and alanine aminotransferase (ALT) levels were assessed. On the V day after transfection, the transfection efficiency in the Hepal-6 cells and the mice livers was 5% and 0.35%, respectively. At 1 wk after HBT, asides from hepatic expression of insulin, the diabetic mice transfected with pcDNA-Pdx1 had a significantly lower sugar (211 +/- 61.6 vs. 413 +/- 62 mg/dL; p = 0.002) level than those transfected with pcDNA; however, the difference diminished afterward. No significant difference in the ALT levels was observed between the 2 groups. No mortality was noted in the mice transfected with pcDNA-Pdx1. The hypoglycemic effect of Pdx1 delivered by HBT was transient and associated with negligible complications. In studies on the short-term biological effects of Pdx1 in vivo, HBT is a potential alternative to viral delivery of Pdx1 to the murine liver.

• 出版日期2009-9
• 单位长春大学