Abstract
CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accmulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity. We showed that bone morphorgeneic protein 4 (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4 treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber formation (56.8±1.3% decrease, P<0.05) and migration (54.6±1.9% decrease, P<0.05) in HUVECs. The in vivo roles of CXXC5 in BMP-signaling-specific vascular development and angiogenesis were shown by specific defect of caudal vein plex vessel formation (57.9±11.8% decrease, P<0.05) in cxxc5 morpholino-injected zebrafish embryos and by supression of BMP4-induced angigogensis in subcutaneously injected Matrigel plugs in CXXC5-/- mice. Overall, CXXC5 is a transcriptional activator for Flk-1, mediating BMP signaling for differentiation and migration of endothelial cell and vessel formation.
| Original language | English |
|---|---|
| Pages (from-to) | 615-626 |
| Number of pages | 12 |
| Journal | FASEB Journal |
| Volume | 28 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2014 Jan 1 |
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Keywords
- Caudal vein plex vessel formation
- HUVECs
- Mouse embryonic stem cells
ASJC Scopus subject areas
- Biochemistry
- Biotechnology
- Genetics
- Molecular Biology
- Medicine(all)
Cite this
CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation. / Kim, Hyun Yi; Yang, Dong Hwa; Shin, Song Weon; Kim, Mi Yeon; Yoon, Jae Hyun; Kim, Suhyun; Park, Hae Chul; Kang, Dong Woo; Min, Dosik; Hur, Man Wook; Choi, Kang Yell.
In: FASEB Journal, Vol. 28, No. 2, 01.01.2014, p. 615-626.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation
AU - Kim, Hyun Yi
AU - Yang, Dong Hwa
AU - Shin, Song Weon
AU - Kim, Mi Yeon
AU - Yoon, Jae Hyun
AU - Kim, Suhyun
AU - Park, Hae Chul
AU - Kang, Dong Woo
AU - Min, Dosik
AU - Hur, Man Wook
AU - Choi, Kang Yell
PY - 2014/1/1
Y1 - 2014/1/1
N2 - CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accmulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity. We showed that bone morphorgeneic protein 4 (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4 treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber formation (56.8±1.3% decrease, P<0.05) and migration (54.6±1.9% decrease, P<0.05) in HUVECs. The in vivo roles of CXXC5 in BMP-signaling-specific vascular development and angiogenesis were shown by specific defect of caudal vein plex vessel formation (57.9±11.8% decrease, P<0.05) in cxxc5 morpholino-injected zebrafish embryos and by supression of BMP4-induced angigogensis in subcutaneously injected Matrigel plugs in CXXC5-/- mice. Overall, CXXC5 is a transcriptional activator for Flk-1, mediating BMP signaling for differentiation and migration of endothelial cell and vessel formation.
AB - CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accmulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity. We showed that bone morphorgeneic protein 4 (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4 treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber formation (56.8±1.3% decrease, P<0.05) and migration (54.6±1.9% decrease, P<0.05) in HUVECs. The in vivo roles of CXXC5 in BMP-signaling-specific vascular development and angiogenesis were shown by specific defect of caudal vein plex vessel formation (57.9±11.8% decrease, P<0.05) in cxxc5 morpholino-injected zebrafish embryos and by supression of BMP4-induced angigogensis in subcutaneously injected Matrigel plugs in CXXC5-/- mice. Overall, CXXC5 is a transcriptional activator for Flk-1, mediating BMP signaling for differentiation and migration of endothelial cell and vessel formation.
KW - Caudal vein plex vessel formation
KW - HUVECs
KW - Mouse embryonic stem cells
UR - http://www.scopus.com/inward/record.url?scp=84897089336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897089336&partnerID=8YFLogxK
U2 - 10.1096/fj.13-236216
DO - 10.1096/fj.13-236216
M3 - Article
VL - 28
SP - 615
EP - 626
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
SN - 1530-6860
IS - 2
ER -