Abstract |
Transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) is currently considered a novel therapeutic strategy for diabetic nephropathy (DN). However, the mechanisms by which UC-MSCs ameliorate renal fibrosis in DN are not well understood. Herein, we firstly investigated the therapeutic effects of mouse UC-MSC infusion on kidney structural and functional impairment in streptozotocin- (STZ-) induced diabetic mice. We found that the repeated injection with mUC-MSCs alleviates albuminuria, glomerulus injury, and fibrosis in DN mouse models. Next, mesangial cells were exposed to 5.6 mM glucose, 30 mM glucose, or mUC-MSC- conditioned medium, and then we performed western blotting, immunofluorescence, wound healing assay, and cell proliferation assay to measure extracellular matrix (ECM) proteins and matrix metalloproteinases ( MMPs), myofibroblast transdifferentiation (MFT), and cell proliferation. We demonstrated that mUC-MSC paracrine decreased the deposition of fibronectin and collagen I by inhibiting TGF-β1-triggered MFT and cell proliferation mediated by PI3K/Akt and MAPK signaling pathways, and elevating the levels of MMP2 and MMP9. Importantly, we provided evidence that the antifibrosis role of mUC-MSC paracrine in DN might be determined by exosomes shed by MSCs. Together, these findings reveal the mechanisms underlying the therapeutic effects of UC-MSCs on renal fibrosis in DN and provide the evidence for DN cell-free therapy based on UC-MSCs in the future.
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Authors | Hongde Li, Pengfei Rong, Xiaoqian Ma, Wei Nie, Yan Chen, Juan Zhang, Qiong Dong, Min Yang, Wei Wang |
Journal | Journal of diabetes research
(J Diabetes Res)
Vol. 2020
Pg. 3847171
( 2020)
ISSN: 2314-6753 [Electronic] England |
PMID | 32455132
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Hongde Li et al. |
Chemical References |
- Matrix Metalloproteinases
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Topics |
- Albuminuria
(metabolism, pathology, therapy)
- Animals
- Cell Line
- Cell Proliferation
(physiology)
- Cell Transdifferentiation
(physiology)
- Diabetes Mellitus, Experimental
(metabolism, pathology)
- Diabetic Nephropathies
(metabolism, pathology, therapy)
- Fibrosis
(metabolism, pathology, therapy)
- Kidney
(metabolism, pathology)
- Matrix Metalloproteinases
(metabolism)
- Mesangial Cells
(metabolism, pathology)
- Mesenchymal Stem Cell Transplantation
- Mesenchymal Stem Cells
- Mice
- Myofibroblasts
(metabolism, pathology)
- Umbilical Cord
(cytology, metabolism)
- Up-Regulation
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