PMID- 19406748
OWN - NLM
STAT- MEDLINE
DCOM- 20090806
LR  - 20220129
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 26
DP  - 2009 Jun 26
TI  - Transforming growth factor-beta promotes recruitment of bone marrow cells and 
      bone marrow-derived mesenchymal stem cells through stimulation of MCP-1 
      production in vascular smooth muscle cells.
PG  - 17564-74
LID - 10.1074/jbc.M109.013987 [doi]
AB  - Bone marrow-derived progenitor cells have recently been shown to be involved in 
      the development of intimal hyperplasia after vascular injury. Transforming growth 
      factor-beta (TGF-beta) has profound stimulatory effects on intimal hyperplasia, 
      but it is unknown whether these effects involve progenitor cell recruitment. In 
      this study we found that although TGF-beta had no direct effect on progenitor 
      cell recruitment, conditioned media derived from vascular smooth muscle cells 
      (VSMC) stimulated with TGF-beta induced migration of both total bone marrow (BM) 
      cells and BM-mesenchymal stem cells (MSC) and also induced MSC differentiation 
      into smooth muscle like cells. Furthermore, overexpression of the signaling 
      molecule Smad3 in VSMC via adenovirus-mediated gene transfer (AdSmad3) enhanced 
      the TGF-beta's chemotactic effect. Microarray analysis of VSMC stimulated by 
      TGF-beta/AdSmad3 revealed monocyte chemoattractant protein-1 (MCP-1) as a likely 
      factor responsible for progenitor cell recruitment. We then demonstrated that 
      TGF-beta through Smad3 phosphorylation induced a robust expression of MCP-1 in 
      VSMC. Recombinant MCP-1 mimicked the stimulatory effect of conditioned media on 
      BM and MSC migration. In the rat carotid injury model, Smad3 overexpression 
      significantly increased MCP-1 expression after vascular injury, consistent with 
      our in vitro results. Interestingly, TGF-beta/Smad3-induced MCP-1 was completely 
      blocked by both Ro-32-0432 and rotterlin, suggesting protein kinase C-delta 
      (PKCdelta) may play a role in TGF-beta/Smad3-induced MCP-1 expression. In 
      summary, our data demonstrate that TGF-beta, through Smad3 and PKCdelta, 
      stimulates VSMC production of MCP-1, which is a chemoattractant for bone 
      marrow-derived cells, specifically MSC. Manipulation of this signaling system may 
      provide a novel approach to inhibition of intimal hyperplasia.
FAU - Zhang, Fan
AU  - Zhang F
AD  - Department of Surgery, University of Wisconsin School of Medicine, Madison, 
      Wisconsin 53705, USA.
FAU - Tsai, Shirling
AU  - Tsai S
FAU - Kato, Kaori
AU  - Kato K
FAU - Yamanouchi, Dai
AU  - Yamanouchi D
FAU - Wang, Chunjie
AU  - Wang C
FAU - Rafii, Shahin
AU  - Rafii S
FAU - Liu, Bo
AU  - Liu B
FAU - Kent, K Craig
AU  - Kent KC
LA  - eng
GR  - F32 HL088818/HL/NHLBI NIH HHS/United States
GR  - F32 HL088818-01/HL/NHLBI NIH HHS/United States
GR  - R01 HL068673/HL/NHLBI NIH HHS/United States
GR  - R01 HL-68673/HL/NHLBI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090430
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
SB  - IM
MH  - Angioplasty, Balloon
MH  - Animals
MH  - Aorta, Thoracic/cytology/metabolism
MH  - Biomarkers/metabolism
MH  - Blotting, Western
MH  - Bone Marrow Cells/*metabolism
MH  - Cell Communication
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors/genetics/*metabolism
MH  - Chemotaxis
MH  - Gene Expression Profiling
MH  - Hyperplasia/metabolism/pathology
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Protein Kinase C-delta/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Smad3 Protein/antagonists & inhibitors/genetics/metabolism
MH  - Stem Cells
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Tunica Intima/metabolism/pathology
PMC - PMC2719395
EDAT- 2009/05/02 09:00
MHDA- 2009/08/07 09:00
PMCR- 2010/06/26
CRDT- 2009/05/02 09:00
PHST- 2009/05/02 09:00 [entrez]
PHST- 2009/05/02 09:00 [pubmed]
PHST- 2009/08/07 09:00 [medline]
PHST- 2010/06/26 00:00 [pmc-release]
AID - S0021-9258(19)82039-2 [pii]
AID - M109.013987 [pii]
AID - 10.1074/jbc.M109.013987 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Jun 26;284(26):17564-74. doi: 10.1074/jbc.M109.013987. Epub 
      2009 Apr 30.