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Therapeutic Effect of Kidney Tubular Cells-Derived Conditioned Medium on the Expression of MicroRNA-377,
Esrafil Mansouri1, Mahmoud Orazizadeh1, Seyyed Ali Mard2
1Department of Anatomical Sciences, Faculty of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Background:
Diabetic nephropathy (DN) is a critical complication of diabetes mellitus. This study evaluates whether administration of conditioned medium from kidney tubular cells (KTCs-CM) has the ability to be efficacious as an alternative to cell-based therapy for DN.
Materials And Methods:
CM of rabbit kidney tubular cells (RK13; KTCs) has been collected and after centrifugation, filtered with 0.2 filters. Four groups of rats have been utilized, including control, DN, DN treated with CM, and sham group. After diabetes induction by streptozotocin (50 mg/kg body weight) in rats, 0.8 ml of the CM was injected to each rat three times per day for 3 consecutive days. Then, 24-h urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) have been measured through detection kits. The histopathological effects of CM on kidneys were evaluated by periodic acid-Schiff staining and the expression of microRNAs (miRNAs) 29a and 377 by using the real-time polymerase chain reaction. The expression of aquapurin-1 (AQP1) protein was also examined by Western blotting.
Results:
Intravenous injections of KTCs-CM significantly reduced the urine volume, protein 24-h, BUN, and Scr, decreased the miRNA-377, and increased miRNA-29a and AQP1 in DN treated with CM rats.
Conclusion:
KTCs-CM may have the potential to prevent kidney injury from diabetes by regulating the microRNAs related to DN and improving the expression of AQP1.
Insights
Conditioned medium from kidney tubular cells (KTCs-CM) shows promise in treating diabetic nephropathy (DN). This therapy reduced key markers of kidney damage and improved specific microRNA and protein levels in diabetic rats.
Area of Science:
- Nephrology
- Endocrinology
- Regenerative Medicine
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes mellitus.
- Current treatments for DN are limited, necessitating novel therapeutic approaches.
- Cell-based therapies show potential but face challenges in clinical application.
Purpose of the Study:
- To evaluate the efficacy of conditioned medium from kidney tubular cells (KTCs-CM) as an alternative to cell-based therapy for DN.
- To investigate the therapeutic potential of KTCs-CM in a rat model of diabetic nephropathy.
Main Methods:
- Collected and filtered conditioned medium from rabbit kidney tubular cells (RK13).
- Induced diabetic nephropathy in rats using streptozotocin.
- Administered KTCs-CM intravenously to DN rats for 3 consecutive days.
- Assessed 24-h urine protein, blood urea nitrogen (BUN), serum creatinine (Scr), kidney histopathology, miRNA-29a and miRNA-377 expression, and aquaporin-1 (AQP1) protein levels.
Main Results:
- KTCs-CM significantly reduced urine volume, 24-h urine protein, BUN, and Scr in DN rats.
- Treatment with KTCs-CM led to decreased expression of miRNA-377 and increased expression of miRNA-29a.
- The expression of AQP1 protein was elevated in DN rats treated with KTCs-CM.
Conclusions:
- KTCs-CM demonstrated significant renoprotective effects in a diabetic nephropathy model.
- The therapeutic benefits of KTCs-CM may be mediated by the regulation of specific microRNAs and aquaporin-1 expression.
- KTCs-CM presents a promising cell-free therapeutic strategy for preventing or treating diabetic kidney injury.
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