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

作者：Chen, Wenbiao^*; Zhang, Feng; Hou, Xianliang; Xu, Huixuan; Tang, Donge^*

来源：Cell Communication and Signaling, 2022, 20(1): 28.

DOI：10.1186/s12964-022-00835-1

• Umbilical cord mesenchymal stem cells
• Extracellular vesicles
• Mesangial proliferative glomerulonephritis
• microRNA-378
• PSMD14
• TGF-beta 1/Smad2/3 signaling pathway

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-beta 1/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-beta 1/Smad2/3 activation. Either miR-378 knockdown or PSMD14 overexpression diminished the protective functions of ucMSC-Evs by activating the TGF-beta 1/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-beta 1/Smad2/3 signaling pathway to reduce tissue hyperplasia and rMC proliferation.

• 单位
  南方医科大学; 1