PMID- 24004644
OWN - NLM
STAT- MEDLINE
DCOM- 20140911
LR  - 20211021
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 4
IP  - 5
DP  - 2013
TI  - Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose 
      via secretion of epithelial growth factor.
PG  - 103
AB  - INTRODUCTION: The apoptosis and subsequent injury of podocytes plays a pathogenic 
      role in diabetic nephropathy (DN). Mesenchymal stem cells (MSCs) are promising 
      therapeutic cells for preventing apoptosis and reducing cellular injury. Our 
      previous study found that MSCs could protect kidneys from diabetes-induced injury 
      without obvious engraftment. So we evaluated the effects of human adipose-derived 
      MSCs (hAd-MSCs) on podocytic apoptosis and injury induced by high glucose (HG) 
      and the underlying mechanisms. METHODS: We used flow cytometry, Western blot and 
      confocal fluorescence microscopy to study podocytic apoptosis and injury induced 
      by HG at 24 hours, 48 hours, and 72 hours in the presence or absence of 
      MSC-conditioned medium (CM). An antibody-based cytokine array was used to 
      identify the mediating factor, which was verified by adding the neutralizing 
      antibody (NtAb) to block its function or adding the recombinant cytokine to the 
      medium to induce its function. RESULTS: hAd-MSC-CM reduced podocytic apoptosis in 
      a dose-dependent manner, decreased the expression of podocytic cleaved caspase-3, 
      and prevented the reduced expression and maintained the normal arrangement of 
      podocytic synaptopodin and nephrin. However, human embryonic lung cell (Wi38)-CM 
      failed to ameliorate podocytic apoptosis or injury. Twelve cytokines with 
      concentration ratios (MSC-CM/Wi38-CM) >10-fold were identified. Epithelial growth 
      factor (EGF) was singled out for its known ability to prevent apoptosis. 
      Recombinant human EGF (rhEGF) prevented podocytic apoptosis and injury similarly 
      to hAd-MSC-CM but, upon blockade of EGF, the beneficial effect of hAd-MSC-CM 
      decreased dramatically. CONCLUSIONS: hAd-MSCs prevent podocytic apoptosis and 
      injury induced by HG, mainly through secreting soluble EG.
FAU - Li, Diangeng
AU  - Li D
FAU - Wang, Nan
AU  - Wang N
FAU - Zhang, Li
AU  - Zhang L
FAU - Hanyu, Zhu
AU  - Hanyu Z
FAU - Xueyuan, Bai
AU  - Xueyuan B
FAU - Fu, Bo
AU  - Fu B
FAU - Shaoyuan, Cui
AU  - Shaoyuan C
FAU - Zhang, Weiguang
AU  - Zhang W
FAU - Xuefeng, Sun
AU  - Xuefeng S
FAU - Li, Rongshan
AU  - Li R
FAU - Chen, Xiangmei
AU  - Chen X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Membrane Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Synaptophysin)
RN  - 0 (nephrin)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 3.4.22.- (Caspase 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Stem Cell Res Ther. 2013;4(5):119. PMID: 24083666
MH  - Adipose Tissue/cytology
MH  - Animals
MH  - Antibodies, Neutralizing/immunology
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/pharmacology
MH  - Cytokines/analysis
MH  - Epidermal Growth Factor/genetics/*metabolism
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Mice
MH  - Podocytes/cytology/*drug effects/metabolism
MH  - Recombinant Proteins/biosynthesis/genetics/pharmacology
MH  - Synaptophysin/metabolism
MH  - Time Factors
PMC - PMC3856604
EDAT- 2013/09/06 06:00
MHDA- 2014/09/12 06:00
PMCR- 2013/09/01
CRDT- 2013/09/06 06:00
PHST- 2012/12/19 00:00 [received]
PHST- 2013/08/02 00:00 [revised]
PHST- 2013/08/23 00:00 [accepted]
PHST- 2013/09/06 06:00 [entrez]
PHST- 2013/09/06 06:00 [pubmed]
PHST- 2014/09/12 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - scrt314 [pii]
AID - 10.1186/scrt314 [doi]
PST - ppublish
SO  - Stem Cell Res Ther. 2013;4(5):103. doi: 10.1186/scrt314.