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

被引：9
作者：
Chen, Wenbiao [1 ,2 ,3 ]
Zhang, Feng [4 ]
Hou, Xianliang [3 ]
Xu, Huixuan [3 ]
Tang, Donge [3 ]
机构：
[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
来源：
CELL COMMUNICATION AND SIGNALING | 2022年 / 20卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Umbilical cord mesenchymal stem cells; Extracellular vesicles; Mesangial proliferative glomerulonephritis; microRNA-378; PSMD14; TGF-beta 1/Smad2/3 signaling pathway; PDGF-D; ANTIBODY; KIDNEY; METASTASIS; INJURY;
D O I：
10.1186/s12964-022-00835-1
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
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页数：17
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