PMID- 25692676
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20211108
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 2
DP  - 2015
TI  - The notch signaling regulates CD105 expression, osteogenic differentiation and 
      immunomodulation of human umbilical cord mesenchymal stem cells.
PG  - e0118168
LID - 10.1371/journal.pone.0118168 [doi]
LID - e0118168
AB  - Mesenchymal stem cells (MSCs) are a group of multipotent cells with key 
      properties of multi-lineage differentiation, expressing a set of relatively 
      specific surface markers and unique immunomodulatory functions. IDO1, a catabolic 
      enzyme of tryptophan, represents a critical molecule mediating immunomodulatory 
      functions of MSCs. However, the signaling pathways involved in regulating these 
      key properties still remain elusive. To investigate the involvement of Notch 
      signaling as well as other potential signaling pathway(s) in regulating these 
      critical properties of MSCs, we treated human umbilical cord-derived mesenchymal 
      stem cells (hUC-MSCs) with gamma-secreatase inhibitor I (GSI-I), which inhibits both 
      Notch signaling and ubiquitin-proteasome activities. It was shown that the GSI-I 
      treatment resulted in apoptosis, reduced expression of surface markers CD73, CD90 
      and CD105, reduced osteogenic differentiation, and reduction of the 
      hUC-MSCs-mediated suppression of Th1 lymphocyte proliferation and the 
      IFN-gamma-induced IDO1 expression. Through distinguishing the effects of GSI-I 
      between Notch inhibition and proteasome inhibition, it was further observed that, 
      whereas both Notch inhibition and proteasome inhibition were attributable to the 
      reduced CD105 expression and osteogenic differentiation, but not to the induced 
      apoptosis. However, Notch inhibition, but not proteasome inhibition, only 
      contributed to the significant effect of GSI-I on Th1 proliferation probably 
      through reducing IDO1 promoter activity. In conclusion, the Notch signaling may 
      represent a very important cell signaling capable of regulating multiple critical 
      properties, especially the immunomodulatory functions of MSCs.
FAU - Na, Tao
AU  - Na T
AD  - Cell Collection and Research Center, National Institutes for Food and Drug 
      Control, Beijing, 100050, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Cell Collection and Research Center, National Institutes for Food and Drug 
      Control, Beijing, 100050, China.
FAU - Zhang, Kehua
AU  - Zhang K
AD  - Cell Collection and Research Center, National Institutes for Food and Drug 
      Control, Beijing, 100050, China.
FAU - Ding, Min
AU  - Ding M
AD  - National Institute for Occupational Safety and Health, Morgantown, West Virginia, 
      26505, United States of America.
FAU - Yuan, Bao-Zhu
AU  - Yuan BZ
AD  - Cell Collection and Research Center, National Institutes for Food and Drug 
      Control, Beijing, 100050, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150218
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, CD)
RN  - 0 (ENG protein, human)
RN  - 0 (Endoglin)
RN  - 0 (IDO1 protein, human)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Notch)
RN  - 0 (benzyloxycarbonyl-leucyl-leucyl-norleucinal)
SB  - IM
MH  - Antigens, CD/*genetics
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Endoglin
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Immunomodulation/drug effects
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*genetics
MH  - Mesenchymal Stem Cells/cytology/drug effects/*physiology
MH  - Oligopeptides/*pharmacology
MH  - Osteogenesis/drug effects
MH  - Receptors, Cell Surface/*genetics
MH  - Receptors, Notch/metabolism
MH  - Signal Transduction/*drug effects
MH  - Th1 Cells/cytology
MH  - Umbilical Cord/*cytology
PMC - PMC4334899
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/02/19 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/02/18
CRDT- 2015/02/19 06:00
PHST- 2014/10/06 00:00 [received]
PHST- 2015/01/08 00:00 [accepted]
PHST- 2015/02/19 06:00 [entrez]
PHST- 2015/02/19 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/02/18 00:00 [pmc-release]
AID - PONE-D-14-30599 [pii]
AID - 10.1371/journal.pone.0118168 [doi]
PST - epublish
SO  - PLoS One. 2015 Feb 18;10(2):e0118168. doi: 10.1371/journal.pone.0118168. 
      eCollection 2015.