1. Combination CTLA-4 immunoglobulin treatment and ultrasound microbubble-mediated exposure improve renal function in a rat model of diabetic nephropathy
- Author
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Yanyan Dong, Chunpeng Zou, Pengfei Wang, Liang Wang, Senmin Wu, Wang Shijia, Chen Xiu, Li Xiuyun, Chao Zheng, and Maosheng Xu
- Subjects
Male ,Aging ,Pathology ,medicine.medical_specialty ,Ultrasonic Therapy ,microbubble ,Immunoglobulins ,Renal function ,Inflammation ,urologic and male genital diseases ,Podocyte ,Rats, Sprague-Dawley ,Nephrin ,Diabetic nephropathy ,Fibrosis ,Animals ,Medicine ,CTLA-4 Antigen ,Diabetic Nephropathies ,sonoporation ,Immune Checkpoint Inhibitors ,Microbubbles ,biology ,ultrasound ,business.industry ,diabetic nephropathy ,Glomerular basement membrane ,Cell Biology ,medicine.disease ,Rats ,cytotoxic T lymphocyte associated antigen 4 immunoglobulin ,Disease Models, Animal ,medicine.anatomical_structure ,Podocin ,biology.protein ,medicine.symptom ,business ,Research Paper - Abstract
Objective: This study explored the therapeutic impact of combined cytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA-4-Ig) treatment and microbubble-mediated exposure in a rat model of diabetic nephropathy (DN). Method: We treated rats using CTLA-4-Ig and/or microbubble exposure. At 8 weeks post-intervention, key parameters were evaluated including blood biochemistry, damage to renal tissue, renal parenchymal elasticity, ultrastructural changes in podocytes, and renal parenchymal expression of CD31, CD34, IL-6, Fn, Collagen I, Talin, Paxillin, α3β1, podocin, nephrin, and B7-1. Result: We found that renal function in the rat model of DN can be significantly improved by CTLA-4-Ig and CTLA-4-Ig + ultrasound microbubble treatment. Treatment efficacy was associated with reductions in renal parenchymal hardness, decreases in podocyte reduction, decreased IL-6, Fn and Collagen I expression, increased Talin, Paxillin and α3β1 expression, elevated podocin and nephrin expression, and decreased B7-1 expression. In contrast, these treatments did not impact CD31 or CD34 expression within the renal parenchyma. Conclusion: These findings clearly emphasize that CTLA-4-Ig can effectively prevent podocyte damage, inhibiting inflammation and fibrosis, and thereby treating and preventing DN. In addition, ultrasound microbubble exposure can improve the ability of CTLA-4-Ig to pass through the glomerular basement membrane in order to access podocytes such that combination CTLA-4-Ig + microbubble exposure treatment is superior to treatment with CTLA-4-Ig only.
- Published
- 2021
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