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

Chen, Wenbiao1,2,3; Zhang, Feng4; Hou, Xianliang3; Xu, Huixuan3; Tang, Donge3

2022-03-09

10.1186/s12964-022-00835-1

CELL COMMUNICATION AND SIGNALING   影响因子和分区

1478-811X

["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."]

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

SCI

英语

通讯

China Postdoctoral Foundation[2021M703372] ; Basic and Applied Basic Research Fund of Guangdong Province[N2021A1515110967] ; National Natural Science Foundation of China[82003172]

Cell Biology

Cell Biology

WOS:000766693000001

BMC

Web of Science

1.Southern Med Univ, Peoples Hosp Longhua, Cent Lab, Affiliated Hosp, Jianshe East Rd, Shenzhen 518109, Guangdong, Peoples R China
2.Southern Med Univ, Peoples Hosp Longhua, Dept Resp Med, Affiliated Hosp, Shenzhen 518109, Guangdong, Peoples R China
3.Jinan Univ, Clin Med Res Ctr, Guangdong Prov Engn Res Ctr Autoimmune Dis Precis, Affiliated Hosp 1,Southern Univ Sci & Technol,Cli, 1017 Dongmen North Rd, Shenzhen 518020, Guangdong, Peoples R China
4.Jinan Univ, Intens Care Unit, Affiliated Hosp 1, Guangzhou 510632, Guangdong, Peoples R China

Chen, Wenbiao,Zhang, Feng,Hou, Xianliang,et al. Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis[J]. CELL COMMUNICATION AND SIGNALING,2022,20(1).

Chen, Wenbiao,Zhang, Feng,Hou, Xianliang,Xu, Huixuan,&Tang, Donge.(2022).Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis.CELL COMMUNICATION AND SIGNALING,20(1).

Chen, Wenbiao,et al."Ameliorating role of microRNA-378 carried by umbilical cord mesenchymal stem cells-released extracellular vesicles in mesangial proliferative glomerulonephritis".CELL COMMUNICATION AND SIGNALING 20.1(2022).