Protein therapy using MafA fused to a polyarginine transduction domain attenuates glucose levels of streptozotocin‑induced diabetic mice.

Abstract

Ectopic expression of musculo aponeurotic fibrosarcoma BZIP transcription factor (Maf) A, has previously been demonstrated to induce insulin expression in non‑β‑cell lines. Protein transduction domains acting as an alternative delivery strategy may deliver heterogeneous proteins into cells. A sequence of 11 arginine residues (11R) has been demonstrated to act as a particularly efficient vector to introduce proteins into various cell types. The present study constructed 11R‑fused MafA to achieve transduction of the protein into cellular membranes and subsequently examined the therapeutic effect of the MafA‑11R protein in streptozotocin‑induced diabetes. A small animal imaging system was used to demonstrate that 11R introduced proteins into cells. The MafA‑11R protein was then injected into the tale vein of healthy male mice, and western blot analysis and immunofluorescence staining was performed to identify the location of the recombinant protein. Ameliorated hyperglycemia in the MafA‑11R‑treated diabetic mice was demonstrated via the improved intraperitoneal glucose tolerance test (IPGTT) and glucose‑stimulated insulin release. Furthermore, insulin producing cells were detected in the jejunum of the MafA‑11R treated mice. The results of the present study indicated that MafA‑11R delivery may act as a novel and potential therapeutic strategy for the future and will not present adverse effects associated with viral vector‑mediated gene therapies.

• Authors: Jun Lu, Lingjing Lin, Huiyue Dong, Xin Meng, Fang Fang, Qinghua Wang, Lianghu Huang, Jianming Tan
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 15 Issue 6 Pg. 4041-4048 (Jun 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 28487936 (Publication Type: Journal Article)

Chemical References

• Basic-Leucine Zipper Transcription Factors
• Blood Glucose
• Insulin
• Peptides
• Recombinant Fusion Proteins
• polyarginine

Topics

• Animals
• Basic-Leucine Zipper Transcription Factors (chemistry, genetics, pharmacology)
• Blood Glucose (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Diabetes Mellitus, Experimental (blood, diagnosis, drug therapy, metabolism)
• Disease Models, Animal
• Glucose Tolerance Test
• Insulin (blood)
• Intestinal Mucosa (metabolism)
• Liver (metabolism)
• Male
• Mice
• Peptides (chemistry)
• Recombinant Fusion Proteins (genetics, pharmacology)
• Tissue Distribution