Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway

Background and aims Diabetic kidney disease (DKD) is one of the most common complications of diabetes. It is reported that mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) may have great clinical application potential for the treatment of DKD, but the underlying mechanism has not been illus...

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Main Authors: Yinghui Wang, Donglin Lu, Shasha Lv, Xiangchun Liu, Gang Liu
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2024.2381597
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author Yinghui Wang
Donglin Lu
Shasha Lv
Xiangchun Liu
Gang Liu
author_facet Yinghui Wang
Donglin Lu
Shasha Lv
Xiangchun Liu
Gang Liu
author_sort Yinghui Wang
collection DOAJ
description Background and aims Diabetic kidney disease (DKD) is one of the most common complications of diabetes. It is reported that mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) may have great clinical application potential for the treatment of DKD, but the underlying mechanism has not been illustrated. To clarify the effect of MSC-Exo on NOD2 signaling pathway in podocytes under high glucose (HG) and DKD, we conduct this study.Methods We co-cultured podocytes and MSCs-Exo under 30 mM HG and injected MSCs-Exo into DKD mice, then we detected the NOD2 signaling pathway by western blot, qRT-PCT, immunofluorescence, transmission electron microscopy and immunohistochemistry both in vitro and in vivo.Results In vitro, HG lead to the apoptosis, increased the ROS level and activated the NOD2 signaling pathway in podocytes, while MSCs-Exo protected podocytes from injury reduced the expression of inflammatory factors including TNF-α, IL-6, IL-1β, and IL-18 and alleviated the inflammatory response, inhibited the activation of NOD2 signaling pathway and the expression of it’s downstream protein p-P65, p-RIP2, prevented apoptosis, increased cell viability in podocytes caused by HG. In vivo, MSCs-Exo alleviated renal injury in DKD mice, protected renal function, decreased urinary albumin excretion and inhibited the activation of NOD2 signaling pathway as well as the inflammation in renal tissue.Conclusion MSCs-Exo protected the podocytes and DKD mice from inflammation by mediating NOD2 pathway, MSCs-Exo may provide a new target for the treatment of DKD.
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spelling doaj-art-bbaa0127c33c4c44864f8e644bb7d43f2025-08-20T02:29:56ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2381597Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathwayYinghui Wang0Donglin Lu1Shasha Lv2Xiangchun Liu3Gang Liu4Department of Nephrology, Multidisciplinary Innovation Center for Nephrology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Nephrology, Multidisciplinary Innovation Center for Nephrology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Nephrology, Multidisciplinary Innovation Center for Nephrology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Nephrology, Multidisciplinary Innovation Center for Nephrology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Nephrology, Multidisciplinary Innovation Center for Nephrology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaBackground and aims Diabetic kidney disease (DKD) is one of the most common complications of diabetes. It is reported that mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) may have great clinical application potential for the treatment of DKD, but the underlying mechanism has not been illustrated. To clarify the effect of MSC-Exo on NOD2 signaling pathway in podocytes under high glucose (HG) and DKD, we conduct this study.Methods We co-cultured podocytes and MSCs-Exo under 30 mM HG and injected MSCs-Exo into DKD mice, then we detected the NOD2 signaling pathway by western blot, qRT-PCT, immunofluorescence, transmission electron microscopy and immunohistochemistry both in vitro and in vivo.Results In vitro, HG lead to the apoptosis, increased the ROS level and activated the NOD2 signaling pathway in podocytes, while MSCs-Exo protected podocytes from injury reduced the expression of inflammatory factors including TNF-α, IL-6, IL-1β, and IL-18 and alleviated the inflammatory response, inhibited the activation of NOD2 signaling pathway and the expression of it’s downstream protein p-P65, p-RIP2, prevented apoptosis, increased cell viability in podocytes caused by HG. In vivo, MSCs-Exo alleviated renal injury in DKD mice, protected renal function, decreased urinary albumin excretion and inhibited the activation of NOD2 signaling pathway as well as the inflammation in renal tissue.Conclusion MSCs-Exo protected the podocytes and DKD mice from inflammation by mediating NOD2 pathway, MSCs-Exo may provide a new target for the treatment of DKD.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2381597Diabetic kidney diseaseexosomesmesenchymal stem cellsNOD2
spellingShingle Yinghui Wang
Donglin Lu
Shasha Lv
Xiangchun Liu
Gang Liu
Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway
Renal Failure
Diabetic kidney disease
exosomes
mesenchymal stem cells
NOD2
title Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway
title_full Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway
title_fullStr Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway
title_full_unstemmed Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway
title_short Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway
title_sort mesenchymal stem cell derived exosomes ameliorate diabetic kidney disease through nod2 signaling pathway
topic Diabetic kidney disease
exosomes
mesenchymal stem cells
NOD2
url https://www.tandfonline.com/doi/10.1080/0886022X.2024.2381597
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AT donglinlu mesenchymalstemcellderivedexosomesamelioratediabetickidneydiseasethroughnod2signalingpathway
AT shashalv mesenchymalstemcellderivedexosomesamelioratediabetickidneydiseasethroughnod2signalingpathway
AT xiangchunliu mesenchymalstemcellderivedexosomesamelioratediabetickidneydiseasethroughnod2signalingpathway
AT gangliu mesenchymalstemcellderivedexosomesamelioratediabetickidneydiseasethroughnod2signalingpathway