Effect of cartilage oligomeric matrix protein angiopoietin-1 on peripheral nerves in db/db diabetic mice
| Autor: | Hong Sun Baek, Sik Lee, Heung Yong Jin, Ming Han Piao, Gou Young Koh, Sung Kwang Park, Ji Hyun Park, Chong Hwa Kim, Tae Sun Park, Won Kim |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Cartilage oligomeric matrix protein
Pharmacology db/db diabetic mice medicine.medical_specialty Diabetic neuropathy peripheral neuropathy biology Epidermis (botany) business.industry Cartilage Nerve fiber COMP-angiopoietin-1 medicine.disease Article medicine.anatomical_structure Peripheral neuropathy Endocrinology Internal medicine Diabetes mellitus Immunology medicine biology.protein Immunohistochemistry Pharmacology (medical) business |
| Zdroj: | Current Therapeutic Research. (4):343-355 |
| ISSN: | 0011-393X |
| DOI: | 10.1016/j.curtheres.2008.08.002 |
| Popis: | Background: Vascular and inflammatory processes have been reported to be factors in the pathogenesis of diabetic neuropathy. Angiopoietin-1 (Ang1) plays essential roles in regulating vascular growth, development, maturation, permeability, and inflammation. Objective: The aim of this study was to investigate the effect of cartilage oligomeric matrix protein (COMP)-Ang1, which is a soluble, stable, potent Ang1 variant, on peripheral nerves in db/db diabetic mice. Methods: The db/db diabetic mice were randomized into 2 groups based on their weight and glucose level and treated with recombinant adenovirus (Ade), expressing either COMP-Ang1 or the β-galactosidase gene (LacZ) (control), for 8 weeks. Immunohistochemistry was performed using a polyclonal antibody of antiprotein gene product and a secondary antibody. Intraepidermal nerve fiber density (IENFD) was quantified as nerve fiber abundance per unit length of epidermis (IENF/mm). In addition, the total capillary length (TCL) per unit length of epidermis was summed (mm/mm2). All slides were coded and the capillary length and the number of nerve fibers were calculated by a blinded observer. Results: Ten diabetic db/db mice (mean [SD] weight, 38.7 [1.95] g) were randomized to receive Ade-COMP-Ang1 or Ade-LacZ. IENFD was significantly greater in the Ade-COMP-Ang1 group compared with the Ade-LacZ group (mean [SD] 8.95 [3.30] vs 3.57 [0.73]/mm; P < 0.05). TCL was also significantly greater in the Ade-COMP-Ang1 group (2.79 [0.99] vs 2.04 [0.58] mm/mm2; P < 0.05). Compared with baseline, fasting blood glucose concentration after 8 weeks of treatment decreased significantly more in the Ade-COMP-Ang1 group than in the Ade-LacZ group (489 [45] to 361 [81] vs 495 [48] to 521 [70] mg/dL; P < 0.05). Conclusions: These results suggest that Ade-COMP-Ang1 might have had proliferative effects on peripheral nerve and cutaneous capillaries in this small animal study. Further investigation of the metabolic effect, target site, and related mediator of COMP-Ang1 is needed. |
| Databáze: | OpenAIRE |
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