Cav‐1 participates in the development of diabetic neuropathy pain through the TLR4 signaling pathway
| Autor: | Jia-Li Chen, Jia-Hui Lu, Yu-Jing Shen, Yan-Nan Cao, Qi Huang, Jun Li, Ci-Shan Xie, Mao-Biao Zhang, Yuan Xiang Tao, Gai-Li Jia, Hong Cao |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Pain Threshold 0301 basic medicine medicine.medical_specialty Diabetic neuropathy Physiology Caveolin 1 Clinical Biochemistry Pain Streptozocin Diabetes Mellitus Experimental Rats Sprague-Dawley 03 medical and health sciences Subcutaneous injection 0302 clinical medicine Lumbar Diabetic Neuropathies Downregulation and upregulation Internal medicine medicine Animals Receptor business.industry Cell Biology Spinal cord medicine.disease Rats Toll-Like Receptor 4 Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 2 Spinal Cord 030220 oncology & carcinogenesis Neuropathic pain TLR4 business Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 235:2060-2070 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.29106 |
| Popis: | This study aims to determine whether caveolin-1 (Cav-1) participates in the process of diabetic neuropathic pain by directly regulating the expression of toll-like receptor 4 (TLR4) and the subsequent phosphorylation of N-methyl-D-aspartate receptor 2B subunit (NR2B) in the spinal cord. Male Sprague-Dawley rats (120-150 g) were continuously fed with high-fat and high-sugar diet for 8 weeks, and received a single low-dose of intraperitoneal streptozocin injection in preparation for the type-II diabetes model. Then, these rats were divided into five groups according to the level of blood glucose, and the mechanical withdrawal threshold and thermal withdrawal latency values. The pain thresholds were measured at 3, 7, and 14 days after animal grouping. Then, eight rats were randomly chosen from each group and killed. Lumbar segments 4-6 of the spinal cord were removed for western blot analysis and immunofluorescence assay. Cav-1 was persistently upregulated in the spinal cord after diabetic neuropathic pain in rats. The downregulation of Cav-1 through the subcutaneous injection of Cav-1 inhibitor daidzein ameliorated the pain hypersensitivity and TLR4 expression in the spinal cord in diabetic neuropathic pain (DNP) rats. Furthermore, it was found that Cav-1 directly bound with TLR4, and the subsequent phosphorylation of NR2B in the spinal cord contributed to the modulation of DNP. These findings suggest that Cav-1 plays a vital role in DNP processing at least in part by directly regulating the expression of TLR4, and through the subsequent phosphorylation of NR2B in the spinal cord. |
| Databáze: | OpenAIRE |
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