Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway

The therapeutic effects and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) on kidney injury in MRL/Ipr mice were studied. UC-MSC, methylprednisolone (MP), and their combination were used to treat MRL/Ipr mice. The therapeutic effects were evaluated by renal function assessment, and HE,...

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Main Authors: Chunkai Huang, Mingyao Meng, Shuo Li, Shiyuan Liu, Lin Li, Yanjun Su, Hui Gao, Shan He, Yiyi Zhao, Min Zhang, Zongliu Hou, Wenju Wang, Xiaodan Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.876054/full
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author Chunkai Huang
Chunkai Huang
Chunkai Huang
Mingyao Meng
Mingyao Meng
Mingyao Meng
Shuo Li
Shuo Li
Shuo Li
Shiyuan Liu
Shiyuan Liu
Shiyuan Liu
Lin Li
Lin Li
Lin Li
Yanjun Su
Hui Gao
Hui Gao
Hui Gao
Shan He
Shan He
Shan He
Yiyi Zhao
Yiyi Zhao
Yiyi Zhao
Min Zhang
Zongliu Hou
Zongliu Hou
Zongliu Hou
Wenju Wang
Wenju Wang
Wenju Wang
Xiaodan Wang
Xiaodan Wang
Xiaodan Wang
author_facet Chunkai Huang
Chunkai Huang
Chunkai Huang
Mingyao Meng
Mingyao Meng
Mingyao Meng
Shuo Li
Shuo Li
Shuo Li
Shiyuan Liu
Shiyuan Liu
Shiyuan Liu
Lin Li
Lin Li
Lin Li
Yanjun Su
Hui Gao
Hui Gao
Hui Gao
Shan He
Shan He
Shan He
Yiyi Zhao
Yiyi Zhao
Yiyi Zhao
Min Zhang
Zongliu Hou
Zongliu Hou
Zongliu Hou
Wenju Wang
Wenju Wang
Wenju Wang
Xiaodan Wang
Xiaodan Wang
Xiaodan Wang
author_sort Chunkai Huang
collection DOAJ
description The therapeutic effects and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) on kidney injury in MRL/Ipr mice were studied. UC-MSC, methylprednisolone (MP), and their combination were used to treat MRL/Ipr mice. The therapeutic effects were evaluated by renal function assessment, and HE, PAS, and Masson staining were carried out on renal tissues and visualized by electron microscopy. Subsequently, podocyte injury was detected by the presence of podocin in renal tissues by immunofluorescence. To further explore the mechanism, serum TGF-β1 was measured, and TGF-β1, p-Smad3, and TRAF6 in the renal tissue were detected by Western blotting. In vitro, TGF-β1 was used to stimulate podocytes, and the podocyte activity and changes in synaptopodin were observed after UC-MSC treatment. Significant improvements in renal function and pathological injury were observed in the UC-MSC group compared to the lupus nephritis (LN) model group. UC-MSC and MP treatment improved podocyte injury in MRL/Ipr mice. Western blot examination showed a significant increase in TGF-β1, p-Smad3, and TRAF6 expression in renal tissues of the LN model group, while significant downregulation of those proteins was observed in the UC-MSC group. After TGF-β1 stimulation in vitro, podocyte activity decreased, and UC-MSC treatment improved podocyte activity and restored synaptopodin expression. UC-MSC therapy could improve the deterioration of renal function and the pathological changes of the renal tissues in MRL/Ipr mice. Our study suggested that UC-MSC may improve kidney injury and podocyte injury in LN mice by inhibiting the TGF-β1 pathway.
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spelling doaj.art-18a43d11a8114ed880944ee05f5b85ee2022-12-22T03:03:05ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-04-011010.3389/fcell.2022.876054876054Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 PathwayChunkai Huang0Chunkai Huang1Chunkai Huang2Mingyao Meng3Mingyao Meng4Mingyao Meng5Shuo Li6Shuo Li7Shuo Li8Shiyuan Liu9Shiyuan Liu10Shiyuan Liu11Lin Li12Lin Li13Lin Li14Yanjun Su15Hui Gao16Hui Gao17Hui Gao18Shan He19Shan He20Shan He21Yiyi Zhao22Yiyi Zhao23Yiyi Zhao24Min Zhang25Zongliu Hou26Zongliu Hou27Zongliu Hou28Wenju Wang29Wenju Wang30Wenju Wang31Xiaodan Wang32Xiaodan Wang33Xiaodan Wang34Scientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaThyroid Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaThyroid Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaScientific Research Department, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, ChinaKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, ChinaYunnan Cell Biology and Clinical Translation Research Center, Kunming, ChinaThe therapeutic effects and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) on kidney injury in MRL/Ipr mice were studied. UC-MSC, methylprednisolone (MP), and their combination were used to treat MRL/Ipr mice. The therapeutic effects were evaluated by renal function assessment, and HE, PAS, and Masson staining were carried out on renal tissues and visualized by electron microscopy. Subsequently, podocyte injury was detected by the presence of podocin in renal tissues by immunofluorescence. To further explore the mechanism, serum TGF-β1 was measured, and TGF-β1, p-Smad3, and TRAF6 in the renal tissue were detected by Western blotting. In vitro, TGF-β1 was used to stimulate podocytes, and the podocyte activity and changes in synaptopodin were observed after UC-MSC treatment. Significant improvements in renal function and pathological injury were observed in the UC-MSC group compared to the lupus nephritis (LN) model group. UC-MSC and MP treatment improved podocyte injury in MRL/Ipr mice. Western blot examination showed a significant increase in TGF-β1, p-Smad3, and TRAF6 expression in renal tissues of the LN model group, while significant downregulation of those proteins was observed in the UC-MSC group. After TGF-β1 stimulation in vitro, podocyte activity decreased, and UC-MSC treatment improved podocyte activity and restored synaptopodin expression. UC-MSC therapy could improve the deterioration of renal function and the pathological changes of the renal tissues in MRL/Ipr mice. Our study suggested that UC-MSC may improve kidney injury and podocyte injury in LN mice by inhibiting the TGF-β1 pathway.https://www.frontiersin.org/articles/10.3389/fcell.2022.876054/fulllupus nephritisumbilical cord mesenchymal stem cellspodocytesTGF-β1p-Smad3TRAF6
spellingShingle Chunkai Huang
Chunkai Huang
Chunkai Huang
Mingyao Meng
Mingyao Meng
Mingyao Meng
Shuo Li
Shuo Li
Shuo Li
Shiyuan Liu
Shiyuan Liu
Shiyuan Liu
Lin Li
Lin Li
Lin Li
Yanjun Su
Hui Gao
Hui Gao
Hui Gao
Shan He
Shan He
Shan He
Yiyi Zhao
Yiyi Zhao
Yiyi Zhao
Min Zhang
Zongliu Hou
Zongliu Hou
Zongliu Hou
Wenju Wang
Wenju Wang
Wenju Wang
Xiaodan Wang
Xiaodan Wang
Xiaodan Wang
Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway
Frontiers in Cell and Developmental Biology
lupus nephritis
umbilical cord mesenchymal stem cells
podocytes
TGF-β1
p-Smad3
TRAF6
title Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway
title_full Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway
title_fullStr Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway
title_full_unstemmed Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway
title_short Umbilical Cord Mesenchymal Stem Cells Ameliorate Kidney Injury in MRL/Ipr Mice Through the TGF-β1 Pathway
title_sort umbilical cord mesenchymal stem cells ameliorate kidney injury in mrl ipr mice through the tgf β1 pathway
topic lupus nephritis
umbilical cord mesenchymal stem cells
podocytes
TGF-β1
p-Smad3
TRAF6
url https://www.frontiersin.org/articles/10.3389/fcell.2022.876054/full
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