Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy
Diabetic nephropathy (DN) is one of the microvascular complications of diabetes. Recent studies suggest that the pyroptosis of renal tubular epithelial cell plays a critical role in DN. Currently, effective therapeutic strategies to counteract and reverse the progression of DN are lacking. Mesenchym...
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Wiley
2023-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2023/5584894 |
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| author | Shuo Zheng Ke Zhang Yaqi Zhang Jing He Yu Ouyang Ruibo Lang Chunchun Ao Yijia Jiang Huan Xiao Yu Li Mao Li Changyong Li Dongcheng Wu |
| author_facet | Shuo Zheng Ke Zhang Yaqi Zhang Jing He Yu Ouyang Ruibo Lang Chunchun Ao Yijia Jiang Huan Xiao Yu Li Mao Li Changyong Li Dongcheng Wu |
| author_sort | Shuo Zheng |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is one of the microvascular complications of diabetes. Recent studies suggest that the pyroptosis of renal tubular epithelial cell plays a critical role in DN. Currently, effective therapeutic strategies to counteract and reverse the progression of DN are lacking. Mesenchymal stem cells (MSCs) represent an attractive therapeutic tool for tissue damage and inflammation owing to their unique immunomodulatory properties. However, the underlying mechanisms remain largely unknown. In the present study, we found that human umbilical cord MSCs (UC-MSCs) can effectively ameliorate kidney damage and reduce inflammation in DN rats. Importantly, UC-MSC treatment inhibits inflammasome-mediated pyroptosis in DN. Mechanistically, we performed RNA sequencing and identified that miR-342-3p was significantly downregulated in the kidneys of DN rats. Furthermore, we found that miR-342-3p was negatively correlated with renal injury and pyroptosis in DN rats. The expression of miR-342-3p was significantly increased after UC-MSC treatment. Moreover, miR-342-3p decreased the expression of Caspase1 by targeting its 3′-UTR, which was confirmed by double-luciferase assay. Using miRNA mimic transfection, we demonstrated that UC-MSC-derived miR-342-3p inhibited pyroptosis of renal tubular epithelial cells through targeting the NLRP3/Caspase1 pathway. These findings would provide a novel intervention strategy for the use of miRNA-modified cell therapy for kidney diseases. |
| format | Article |
| id | doaj-art-e9241cd4698f49d2966d4a0cb2d79c7c |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-e9241cd4698f49d2966d4a0cb2d79c7c2025-08-20T03:24:38ZengWileyStem Cells International1687-96782023-01-01202310.1155/2023/5584894Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic NephropathyShuo Zheng0Ke Zhang1Yaqi Zhang2Jing He3Yu Ouyang4Ruibo Lang5Chunchun Ao6Yijia Jiang7Huan Xiao8Yu Li9Mao Li10Changyong Li11Dongcheng Wu12Department of Biochemistry and Molecular BiologyDepartment of Biochemistry and Molecular BiologyDepartment of Biochemistry and Molecular BiologyDepartment of Biochemistry and Molecular BiologyDepartment of Biochemistry and Molecular BiologyDepartment of Biochemistry and Molecular BiologyDepartment of Biochemistry and Molecular BiologyDepartment of Biochemistry and Molecular BiologySchool of Life ScienceSchool of Life ScienceSchool of Life ScienceDepartment of PhysiologyDepartment of Biochemistry and Molecular BiologyDiabetic nephropathy (DN) is one of the microvascular complications of diabetes. Recent studies suggest that the pyroptosis of renal tubular epithelial cell plays a critical role in DN. Currently, effective therapeutic strategies to counteract and reverse the progression of DN are lacking. Mesenchymal stem cells (MSCs) represent an attractive therapeutic tool for tissue damage and inflammation owing to their unique immunomodulatory properties. However, the underlying mechanisms remain largely unknown. In the present study, we found that human umbilical cord MSCs (UC-MSCs) can effectively ameliorate kidney damage and reduce inflammation in DN rats. Importantly, UC-MSC treatment inhibits inflammasome-mediated pyroptosis in DN. Mechanistically, we performed RNA sequencing and identified that miR-342-3p was significantly downregulated in the kidneys of DN rats. Furthermore, we found that miR-342-3p was negatively correlated with renal injury and pyroptosis in DN rats. The expression of miR-342-3p was significantly increased after UC-MSC treatment. Moreover, miR-342-3p decreased the expression of Caspase1 by targeting its 3′-UTR, which was confirmed by double-luciferase assay. Using miRNA mimic transfection, we demonstrated that UC-MSC-derived miR-342-3p inhibited pyroptosis of renal tubular epithelial cells through targeting the NLRP3/Caspase1 pathway. These findings would provide a novel intervention strategy for the use of miRNA-modified cell therapy for kidney diseases.http://dx.doi.org/10.1155/2023/5584894 |
| spellingShingle | Shuo Zheng Ke Zhang Yaqi Zhang Jing He Yu Ouyang Ruibo Lang Chunchun Ao Yijia Jiang Huan Xiao Yu Li Mao Li Changyong Li Dongcheng Wu Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy Stem Cells International |
| title | Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy |
| title_full | Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy |
| title_fullStr | Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy |
| title_full_unstemmed | Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy |
| title_short | Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy |
| title_sort | human umbilical cord mesenchymal stem cells inhibit pyroptosis of renal tubular epithelial cells through mir 342 3p caspase1 signaling pathway in diabetic nephropathy |
| url | http://dx.doi.org/10.1155/2023/5584894 |
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