PMID- 20822188
OWN - NLM
STAT- MEDLINE
DCOM- 20110704
LR  - 20110419
IS  - 1554-8937 (Electronic)
IS  - 1554-8929 (Linking)
VI  - 5
IP  - 11
DP  - 2010 Nov 19
TI  - Role of Hmbox1 in endothelial differentiation of bone-marrow stromal cells by a 
      small molecule.
PG  - 1035-43
LID - 10.1021/cb100153r [doi]
AB  - Bone marrow stromal cells (BMSCs) play critical roles in repairing endothelium 
      damage. However, the mechanisms underlying BMSC differentiation into vascular 
      endothelial cells (VECs) is not well understood. We aimed to find new factors 
      involved in this process by exploiting a novel chemical inducer in a gene 
      microarray assay. We first identified a novel benzoxazine derivative 
      (6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine; ABO) that can induce BMSC 
      differentiation to VECs in a capillary-like tube formation assay, promote 
      analysis of endothelial cell-specific marker expression, and facilitate uptake of 
      1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-acetylated 
      low-density lipoprotein (Dil-Ac-LDL). Microarray analysis of BMSCs treated with 
      ABO for 4 h revealed changes in only a handful of genes. The only one upregulated 
      was homeobox-containing 1 (Hmbox1) gene, whereas six genes, including IP-10 and 
      others, were downregulated. The upregulation of Hmbox1 and downregulation of 
      IP-10 were confirmed by RT-PCR, quantitative PCR (qPCR), and Western blot 
      analysis. It is reported that IP-10 could suppresse EC differentiation into 
      capillary structures. In this study ABO could not induce BMSC differentiation to 
      VECs in the presence of IP-10. Small interfering RNA knockdown of Hmbox1 blocked 
      ABO-induced BMSC differentiation and increased the level of IP-10 but decreased 
      Ets-1. Thus, ABO is a novel inducer for BMSC differentiation to VECs, and Hmbox1 
      is a key factor in the differentiation. IP-10 and Ets-1 might be relevant targets 
      of Hmbox1 in BMSC differentiation to VECs. These findings provide information on 
      a novel target and a new platform for further investigating the gene control of 
      BMSC differentiation to VECs.
FAU - Su, Le
AU  - Su L
AD  - Institute of Developmental Biology, School of Life Science, Shandong University, 
      Jinan 250100, China.
FAU - Zhao, HongLing
AU  - Zhao H
FAU - Sun, ChunHui
AU  - Sun C
FAU - Zhao, BaoXiang
AU  - Zhao B
FAU - Zhao, Jing
AU  - Zhao J
FAU - Zhang, ShangLi
AU  - Zhang S
FAU - Su, Hua
AU  - Su H
FAU - Miao, JunYing
AU  - Miao J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - ACS Chem Biol
JT  - ACS chemical biology
JID - 101282906
RN  - 0 (6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine)
RN  - 0 (Benzoxazines)
RN  - 0 (Hmbox1 protein, rat)
RN  - 0 (Homeodomain Proteins)
SB  - IM
MH  - Animals
MH  - Benzoxazines/*pharmacology
MH  - Bone Marrow Cells/*cytology/drug effects
MH  - Cell Differentiation/drug effects/genetics/*physiology
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*cytology/physiology
MH  - Gene Expression Regulation/drug effects
MH  - Homeodomain Proteins/agonists/genetics/*physiology
MH  - Male
MH  - Neovascularization, Physiologic/drug effects/genetics/*physiology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Stromal Cells/cytology/drug effects/physiology
EDAT- 2010/09/09 06:00
MHDA- 2011/07/05 06:00
CRDT- 2010/09/09 06:00
PHST- 2010/09/09 06:00 [entrez]
PHST- 2010/09/09 06:00 [pubmed]
PHST- 2011/07/05 06:00 [medline]
AID - 10.1021/cb100153r [doi]
PST - ppublish
SO  - ACS Chem Biol. 2010 Nov 19;5(11):1035-43. doi: 10.1021/cb100153r.