Intramuscular delivery of a naked DNA plasmid encoding proinsulin and pancreatic regenerating III protein ameliorates type 1 diabetes mellitus
| Autor: | Hongjie Wang, Sheng-Nan Xie, Sha-Sha Zhang, Wen-Rui Hou, Lu-Lu Li, Yu-Yong Su, Jingli Lu, Ming Xiang |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty endocrine system diseases Genetic enhancement Gene Expression Biology Injections Intramuscular T-Lymphocytes Regulatory Streptozocin Mice Internal medicine Chlorocebus aethiops medicine Animals Insulin IL-2 receptor Pancreas Proinsulin Pharmacology Mice Inbred BALB C Pancreatic islets nutritional and metabolic diseases FOXP3 Proteins DNA Genetic Therapy medicine.disease Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 1 Naked DNA Hyperglycemia COS Cells Insulitis Plasmids |
| Zdroj: | Pharmacological research. 63(4) |
| ISSN: | 1096-1186 |
| Popis: | Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of β cells. Up to now, there is still no cure for this devastating disease and alternative approach should be developed. To explore a novel gene therapy strategy combining immunotherapy and β cell regeneration, we constructed a non-viral plasmid encoding proinsulin (PI) and pancreatic regenerating (Reg) III protein (pReg/PI). Therapeutic potentials of this plasmid for T1DM were investigated. Intramuscular delivery of pReg/PI resulted in a significant reduction in hyperglycemia and diabetes incidence, with an increased insulin contents in the serum of T1DM mice model induced by STZ. Treatment with pReg/PI also restored the balance of Th1/Th2 cytokines and expanded CD4(+)CD25(+)Foxp3(+) T regulatory cells, which may attribute to the establishment of self-immune tolerance. Additionally, in comparison to the mice treated with empty vector pBudCE4.1 (pBud), attenuated insulitis and apoptosis achieved by inhibiting activation of NF-κB in the pancreas of pReg/PI treated mice were observed. In summary, these results indicate that intramuscular delivery of pReg/PI distinctly ameliorated STZ-induced T1DM by reconstructing the immunological self-tolerance and promoting the regeneration of β cells, which might be served as a promising candidate for the gene therapy of T1DM. |
| Databáze: | OpenAIRE |
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