Receptor for Advanced Glycation End Products (RAGEs) and Experimental Diabetic Neuropathy
| Autor: | Minh Dang Nguyen, Fei Song, Ann Marie Schmidt, Christina Yang, Ling Ling Rong, Wei Liu, Jose A. Martinez, Douglas W. Zochodne, Cory Toth, Noor Ramji, Valentine Brussee, Jeff Durand |
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| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Diabetic neuropathy endocrine system diseases Endocrinology Diabetes and Metabolism Receptor for Advanced Glycation End Products Neural Conduction Diabetes Mellitus Experimental RAGE (receptor) Mice Diabetic Neuropathies Glycation Ganglia Spinal Diabetes mellitus Internal medicine Internal Medicine medicine Animals Receptors Immunologic Crosses Genetic Protein kinase C Mice Knockout business.industry medicine.disease Sciatic Nerve Mice Inbred C57BL Peripheral neuropathy Endocrinology medicine.anatomical_structure Peripheral nervous system Disease Progression Signal transduction business |
| Zdroj: | Diabetes. 57:1002-1017 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db07-0339 |
| Popis: | OBJECTIVE— Heightened expression of the receptor for advanced glycation end products (RAGE) contributes to development of systemic diabetic complications, but its contribution to diabetic neuropathy is uncertain. We studied experimental diabetic neuropathy and its relationship with RAGE expression using streptozotocin-induced diabetic mice including a RAGE−/− cohort exposed to long-term diabetes compared with littermates without diabetes. RESEARCH DESIGN AND METHODS— Structural indexes of neuropathy were addressed with serial (1, 3, 5, and 9 months of experimental diabetes) electrophysiological and quantitative morphometric analysis of dorsal root ganglia (DRG), peripheral nerve, and epidermal innervation. RAGE protein and mRNA levels in DRG, peripheral nerve, and epidermal terminals were assessed in WT and RAGE−/− mice, with and without diabetes. The correlation of RAGE activation with nuclear factor (NF)-κB and protein kinase C βII (PKCβII) protein and mRNA expression was also determined. RESULTS— Diabetic peripheral epidermal axons, sural axons, Schwann cells, and sensory neurons within ganglia developed dramatic and cumulative rises in RAGE mRNA and protein along with progressive electrophysiological and structural abnormalities. RAGE−/− mice had attenuated structural features of neuropathy after 5 months of diabetes. RAGE-mediated signaling pathway activation for NF-κB and PKCβII pathways was most evident among Schwann cells in the DRG and peripheral nerve. CONCLUSIONS— In a long-term model of experimental diabetes resembling human diabetic peripheral neuropathy, RAGE expression in the peripheral nervous system rises cumulatively and relates to progressive pathological changes. Mice lacking RAGE have attenuated features of neuropathy and limited activation of potentially detrimental signaling pathways. |
| Databáze: | OpenAIRE |
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