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DIABETOLOGY / EXPERIMENTAL RESEARCH
Mesenchymal stem cells suppress kidney injury molecule-1 associated with inhibition of renal PKC/NF-Kβ/STAT3 fibrotic signaling pathway in rats with diabetic nephropathy
1
Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
2
Department of Child Health, College of Medicine, King Khalid University, Abha, Saudi Arabia
3
Department of Internal Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia
4
Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia
5
Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo, Egypt
6
Department of Medical Histology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo, Egypt
Submission date: 2024-03-22
Final revision date: 2024-07-04
Acceptance date: 2024-07-07
Online publication date: 2024-07-28
Corresponding author
Amal Dawood
Department of Basic Medical Sciences College of Medicine Princess Nourah bint Abdulrahman University P.O. Box 84428 Riyadh 11671 Saudi Arabia
Department of Basic Medical Sciences College of Medicine Princess Nourah bint Abdulrahman University P.O. Box 84428 Riyadh 11671 Saudi Arabia
Arch Med Sci 2025;21(4):1577-1591
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Diabetes is the predominant etiology behind end-stage kidney disease, commonly referred to as renal failure. The intricate relationships among oxidative stress, inflammation, and renal fibrotic changes in diabetes-induced nephropathy, particularly in instances involving and not involving the administration of mesenchymal stem cells (MSCs), remain a subject less explored in existing research.
Material and methods:
Twenty-four male Wistar rats (180 and 200 g) were randomly assigned to one of three groups (n = 8). The control group received standard laboratory chow, and the groups with type 2 diabetes mellitus (T2DM) received a single dose of streptozotocin, 45 mg/kg, after 3 weeks of pretreatment with a high-fat diet (HFD). Rats with T2DM were split into the T2DM model group and bone marrow (BM) mesenchymal stem cells (MSC) treated group (T2DM + MSCs) 8 weeks after DM was confirmed. BM-MSCs were injected systemically at doses of 2 × 106 cells/rat.
Results:
Diabetes significantly altered oxidative stress (MDA, SOD), inflammation (TNF-α, IL-6), and kidney injury (KIM-1, NAGAL) biomarkers, a modulation that was mitigated by MSCs (p < 0.0001). Furthermore, diabetes-induced kidney fibrosis showed a noteworthy reduction in the presence of MSCs. A notable correlation emerged between body weight, systolic blood pressure (SBP), oxidative stress, inflammation, fibrosis, the PKC/NF-KB/STAT-3 axis, and hyperglycemia.
Conclusions:
Our results suggest that diabetes is associated with elevated oxidative stress, inflammation, biomarkers of kidney injury, upregulation of the renal PKC/NF-KB/STAT-3 pathway, and hypertension, all of which are countered by MSC intervention.
Diabetes is the predominant etiology behind end-stage kidney disease, commonly referred to as renal failure. The intricate relationships among oxidative stress, inflammation, and renal fibrotic changes in diabetes-induced nephropathy, particularly in instances involving and not involving the administration of mesenchymal stem cells (MSCs), remain a subject less explored in existing research.
Material and methods:
Twenty-four male Wistar rats (180 and 200 g) were randomly assigned to one of three groups (n = 8). The control group received standard laboratory chow, and the groups with type 2 diabetes mellitus (T2DM) received a single dose of streptozotocin, 45 mg/kg, after 3 weeks of pretreatment with a high-fat diet (HFD). Rats with T2DM were split into the T2DM model group and bone marrow (BM) mesenchymal stem cells (MSC) treated group (T2DM + MSCs) 8 weeks after DM was confirmed. BM-MSCs were injected systemically at doses of 2 × 106 cells/rat.
Results:
Diabetes significantly altered oxidative stress (MDA, SOD), inflammation (TNF-α, IL-6), and kidney injury (KIM-1, NAGAL) biomarkers, a modulation that was mitigated by MSCs (p < 0.0001). Furthermore, diabetes-induced kidney fibrosis showed a noteworthy reduction in the presence of MSCs. A notable correlation emerged between body weight, systolic blood pressure (SBP), oxidative stress, inflammation, fibrosis, the PKC/NF-KB/STAT-3 axis, and hyperglycemia.
Conclusions:
Our results suggest that diabetes is associated with elevated oxidative stress, inflammation, biomarkers of kidney injury, upregulation of the renal PKC/NF-KB/STAT-3 pathway, and hypertension, all of which are countered by MSC intervention.
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