PMID- 24480247
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20211021
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 5
IP  - 1
DP  - 2014 Jan 30
TI  - Glutathione S-transferase Mu 2-transduced mesenchymal stem cells ameliorated 
      anti-glomerular basement membrane antibody-induced glomerulonephritis by 
      inhibiting oxidation and inflammation.
PG  - 19
LID - 10.1186/scrt408 [doi]
AB  - INTRODUCTION: Oxidative stress is implicated in tissue inflammation, and plays an 
      important role in the pathogenesis of immune-mediated nephritis. Using the 
      anti-glomerular basement membrane antibody-induced glomerulonephritis 
      (anti-GBM-GN) mouse model, we found that increased expression of glutathione 
      S-transferase Mu 2 (GSTM2) was related to reduced renal damage caused by anti-GBM 
      antibodies. Furthermore, mesenchymal stem cell (MSC)-based therapy has shed light 
      on the treatment of immune-mediated kidney diseases. The aim of this study was to 
      investigate if MSCs could be utilized as vehicles to deliver the GSTM2 gene 
      product into the kidney and to evaluate its potential therapeutic effect on 
      anti-GBM-GN. METHODS: The human GSTM2 gene (hGSTM2) was transduced into mouse 
      bone marrow-derived MSCs via a lentivirus vector to create a stable cell line 
      (hGSTM2-MSC). The cultured hGSTM2-MSCs were treated with 0.5 mM H2O2, and 
      apoptotic cells were measured by terminal dUTP nick-end labeling (TUNEL) assay. 
      The 129/svj mice, which were challenged with anti-GBM antibodies, were injected 
      with 10(6) hGSTM2-MSCs via the tail vein. Expression of hGSTM2 and inflammatory 
      cytokines in the kidney was assayed by quantitative PCR and western blotting. 
      Renal function of mice was evaluated by monitoring proteinuria and levels of 
      blood urea nitrogen (BUN), and renal pathological changes were analyzed by 
      histochemistry. Immunohistochemical analysis was performed to measure 
      inflammatory cell infiltration and renal cell apoptosis. RESULTS: MSCs transduced 
      with hGSTM2 exhibited similar growth and differentiation properties to MSCs. 
      hGSTM2-MSCs persistently expressed hGSTM2 and resisted H2O2-induced apoptosis. 
      Upon injection into 129/svj mice, hGSTM2-MSCs migrated to the kidney and 
      expressed hGSTM2. The anti-GBM-GN mice treated with hGSTM2-MSCs exhibited reduced 
      proteinuria and BUN (58% and 59% reduction, respectively) and ameliorated renal 
      pathological damage, compared with control mice. Mice injected with hGSTM2-MSCs 
      showed alleviated renal inflammatory cell infiltration and reduced expression of 
      chemokine (C-C motif) ligand 2 (CCL2), interleukin (IL)-1beta and IL-6 (53%, 46% and 
      52% reduction, respectively), compared with controls. Moreover, hGSTM2-MSCs 
      increased expression of renal superoxide dismutase and catalase, which may 
      associate with detoxifying reactive oxygen species to prevent oxidative renal 
      damage. CONCLUSIONS: Our data suggest that the enhanced protective effect of 
      GSTM2-transduced MSCs against anti-GBM-GN might be associated with inhibition of 
      oxidative stress-induced renal cell apoptosis and inflammation, through 
      over-expression of hGSTM2 in mouse kidneys.
FAU - Li, Yajuan
AU  - Li Y
FAU - Yan, Mei
AU  - Yan M
FAU - Yang, Jichen
AU  - Yang J
FAU - Raman, Indu
AU  - Raman I
FAU - Du, Yong
AU  - Du Y
FAU - Min, Soyoun
AU  - Min S
FAU - Fang, Xiangdong
AU  - Fang X
FAU - Mohan, Chandra
AU  - Mohan C
FAU - Li, Quan-Zhen
AU  - Li QZ
LA  - eng
GR  - P50 AR055503/AR/NIAMS NIH HHS/United States
GR  - R03 AR055778/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140130
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Autoantibodies)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.5.1.18 (glutathione S-transferase Mu 2)
SB  - IM
MH  - Animals
MH  - Autoantibodies/immunology
MH  - *Genetic Therapy
MH  - Glomerular Basement Membrane/immunology/metabolism
MH  - Glomerulonephritis, Membranous/*genetics/immunology/metabolism
MH  - Glutathione Transferase/*genetics/immunology/metabolism
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred DBA
MH  - *Oxidative Stress
PMC - PMC4055015
EDAT- 2014/02/01 06:00
MHDA- 2015/05/13 06:00
PMCR- 2014/01/30
CRDT- 2014/02/01 06:00
PHST- 2013/07/05 00:00 [received]
PHST- 2014/01/15 00:00 [accepted]
PHST- 2014/02/01 06:00 [entrez]
PHST- 2014/02/01 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
PHST- 2014/01/30 00:00 [pmc-release]
AID - scrt408 [pii]
AID - 10.1186/scrt408 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2014 Jan 30;5(1):19. doi: 10.1186/scrt408.