Dataset Information

Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis.

ABSTRACT:

Background

Mesenchymal stem cells (MSCs) and their released extracellular vesicles (Evs) have shown protective effects against kidney diseases. This study aims to study the functions of umbilical cord MSCs-released Evs (ucMSC-Evs) and their implicated molecules in mesangial proliferative glomerulonephritis (MsPGN).

Methods

A rat model of MsPGN was induced by anti-Thy-1.1, and rat mesangial cells (rMCs) HBZY-1 were treated with PDGF-BB/DD to mimic MsPGN condition in vitro. Rats and cells were treated with different doses of ucMSC-Evs, and then the pathological changes in renal tissues and proliferation of rMCs were determined. Differentially expressed microRNAs (miRNAs) after Evs treatment were screened by microarray analysis. The interactions among miR-378, PSMD14, and TGFBR1 were analyzed. Gain- and loss-of function studies of miR-378 and PSMD14 were performed to explore their effects on tissue hyperplasia and rMC proliferation and their interactions with the TGF-β1/Smad2/3 signaling pathway.

Results

The ucMSC-Evs treatment ameliorated mesangial hyperplasia and fibrosis in rat renal tissues and suppressed the aberrant proliferation of rMCs in a dose-dependent manner. miR-378 was the most upregulated miRNA in tissues and cells after ucMSC-Evs treatment. miR-378 directly targeted PSMD14, and PSMD14 maintained the stability of TGFBR1 through deubiquitination modification, which led to TGF-β1/Smad2/3 activation. Either miR-378 knockdown or PSMD14 overexpression diminished the protective functions of ucMSC-Evs by activating the TGF-β1/Smad2/3 signaling pathway.

Conclusion

UcMSC-Evs ameliorate pathological process in MsPGN through the delivery of miR-378, which suppresses PSMD14-mediated TGFBR1 stability and inactivates the TGF-β1/Smad2/3 signaling pathway to reduce tissue hyperplasia and rMC proliferation. Video abstract.

SUBMITTER: Chen W

PROVIDER: S-EPMC8905735 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis.

Chen Wenbiao W Zhang Feng F Hou Xianliang X Xu Huixuan H Tang Donge D

Cell communication and signaling : CCS 20220309 1

<h4>Background</h4>Mesenchymal stem cells (MSCs) and their released extracellular vesicles (Evs) have shown protective effects against kidney diseases. This study aims to study the functions of umbilical cord MSCs-released Evs (ucMSC-Evs) and their implicated molecules in mesangial proliferative glomerulonephritis (MsPGN).<h4>Methods</h4>A rat model of MsPGN was induced by anti-Thy-1.1, and rat mesangial cells (rMCs) HBZY-1 were treated with PDGF-BB/DD to mimic MsPGN condition in vitro. Rats and ...[more]

PMID: 35264186

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Dataset Information

Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis.

Background

Methods

Results

Conclusion

Publications

Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis.

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