IMR Press / FBL / Volume 28 / Issue 9 / DOI: 10.31083/j.fbl2809203
Open Access Original Research
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Diabetic Kidney Disease in Rats by Inhibiting Apoptosis and Inflammation
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1 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China
2 Department of Cardiology, The Second Affiliated Hospital of Shandong First Medical University, 271000 Taian, Shandong, China
*Correspondence: Tjfbama@163.com (Jinfan Tian); Cjge1116@163.com (Changjiang Ge); song0929@mail.ccmu.edu.cn (Xiantao Song)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(9), 203; https://doi.org/10.31083/j.fbl2809203
Submitted: 15 November 2022 | Revised: 15 February 2023 | Accepted: 27 February 2023 | Published: 14 September 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background and Aims: Previous studies have confirmed the anti-inflammation effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo). We aimed to investigate the therapeutic effect of BMSC-Exo on diabetic kidney disease (DKD), as well as the underlying mechanisms. Methods: SD rats were induced by streptozotocin combined with a high-fat diet to establish a diabetes disease model. BMSCs-Exo were injected via tail veins at a weekly dose of 100 µg for 12 weeks. Pathological changes in the rat kidneys were evaluated using HE, Masson, and Periodic Acid-Schiff and immunohistochemical staining. TUNEL staining and western blot were used to evaluate the expression levels of apoptosis-related proteins in the rat kidney cells. The TNF-α level was detected by PCR and NF-κB (p65) by western blotting to examine the inflammatory responses in the renal tissue. Results: BMSCs-Exo significantly alleviated the renal structural damage and the distribution of apoptotic cells in diabetic rats. Furthermore, BMSCs-Exo increased the expression of pro-apoptosis protein Bax and decreased the expression of apoptosis-executing protein Cleaved Caspase 9 and Cleaved caspase 3. In addition, the transcription level of TNF-α in kidney tissue and NF-κB (p65) expression was also decreased through BMSCs-Exo treatment. Besides, the levels of glucose (GLU), creatinine (Cr), and burea nitrogen (BUN) in diabetic rats were decreased by the BMSC-Exo treatment. Conclusions: BMSCs-Exo may alleviate diabetic kidney damage by inhibiting apoptosis and inflammation.

Keywords
diabetic kidney disease
bone marrow mesenchymal stem cells
exosome
apoptosis
inflammation
Funding
Z161100000516139/Beijing Municipal Science and Technology Project
82270341/National Nature Science Foundation
82270341/National Nature Science Foundation
QML20210603/‘qingmiao’ plan
2022-1-2061/Capital Health Research and Development of Special
Figures
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