PMID- 24595007
OWN - NLM
STAT- MEDLINE
DCOM- 20150109
LR  - 20211203
IS  - 1876-7753 (Electronic)
IS  - 1873-5061 (Linking)
VI  - 12
IP  - 3
DP  - 2014 May
TI  - Serotonin augments smooth muscle differentiation of bone marrow stromal cells.
PG  - 599-609
LID - S1873-5061(14)00012-9 [pii]
LID - 10.1016/j.scr.2014.02.003 [doi]
AB  - Bone marrow stromal cells (BMSCs) contain a subset of multipotent stem cells. 
      Here, we demonstrate that serotonin, a biogenic amine released by platelets and 
      mast cells, can induce the smooth muscle differentiation of BMSCs. Brown Norway 
      rat BMSCs stimulated with serotonin had increased expression of the smooth muscle 
      markers smooth muscle myosin heavy chain (MHC) and alpha actin (alpha-SMA) by qPCR and 
      Western blot, indicating smooth muscle differentiation. This was accompanied by a 
      concomitant down-regulation of the microRNA miR-25-5p, which was found to 
      negatively regulate smooth muscle differentiation. Serotonin upregulated serum 
      response factor (SRF) and myocardin, transcription factors known to induce 
      contractile protein expression in smooth muscle cells, while it down-regulated 
      Elk1 and Kruppel-like factor 4 (KLF4), known to induce proliferation. Serotonin 
      increased SRF binding to promoter regions of the MHC and alpha-SMA genes, assessed by 
      chromatin immunoprecipitation assay. Induction of smooth muscle differentiation 
      by serotonin was blocked by the knock-down of SRF and myocardin. Transforming 
      growth factor (TGF)-beta1 was constitutively expressed by BMSCs and serotonin 
      triggered its release. Inhibition of miR-25-5p augmented TGF-beta1 expression, 
      however the differentiation of BMSCs was not mediated by TGF-beta1. These findings 
      demonstrate that serotonin promotes a smooth muscle-like phenotype in BMSCs by 
      altering the balance of SRF, myocardin, Elk1 and KLF4 and miR-25-5p is involved 
      in modulating this balance. Therefore, serotonin potentially contributes to the 
      pathogenesis of diseases characterized by tissue remodeling with increased smooth 
      muscle mass.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Hirota, Nobuaki
AU  - Hirota N
AD  - Meakins-Christie Laboratories, Department of Medicine, McGill University, 3626 
      St.-Urbain, Montreal, Quebec, H2X 2P2, Canada.
FAU - McCuaig, Sarah
AU  - McCuaig S
AD  - Meakins-Christie Laboratories, Department of Medicine, McGill University, 3626 
      St.-Urbain, Montreal, Quebec, H2X 2P2, Canada.
FAU - O'Sullivan, Michael J
AU  - O'Sullivan MJ
AD  - Meakins-Christie Laboratories, Department of Medicine, McGill University, 3626 
      St.-Urbain, Montreal, Quebec, H2X 2P2, Canada.
FAU - Martin, James G
AU  - Martin JG
AD  - Meakins-Christie Laboratories, Department of Medicine, McGill University, 3626 
      St.-Urbain, Montreal, Quebec, H2X 2P2, Canada. Electronic address: 
      james.martin@mcgill.ca.
LA  - eng
GR  - MOP77749/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140213
PL  - England
TA  - Stem Cell Res
JT  - Stem cell research
JID - 101316957
RN  - 0 (Klf4 protein, rat)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (MicroRNAs)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Serum Response Factor)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (myocardin)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Animals
MH  - *Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Kruppel-Like Factor 4
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/metabolism
MH  - MicroRNAs/genetics/metabolism
MH  - Myocytes, Smooth Muscle/cytology/*metabolism
MH  - Nuclear Proteins/genetics/metabolism
MH  - Rats
MH  - Serotonin/genetics/*metabolism
MH  - Serum Response Factor/genetics/metabolism
MH  - Trans-Activators/genetics/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - Up-Regulation
EDAT- 2014/03/07 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/03/06 06:00
PHST- 2014/01/23 00:00 [received]
PHST- 2014/02/05 00:00 [revised]
PHST- 2014/02/05 00:00 [accepted]
PHST- 2014/03/06 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - S1873-5061(14)00012-9 [pii]
AID - 10.1016/j.scr.2014.02.003 [doi]
PST - ppublish
SO  - Stem Cell Res. 2014 May;12(3):599-609. doi: 10.1016/j.scr.2014.02.003. Epub 2014 
      Feb 13.