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Transcriptional activation of endoglin and transforming growth factor-? signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury

Transcriptional activation of endoglin and transforming growth factor-? signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury
Transcriptional activation of endoglin and transforming growth factor-? signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury
Endoglin is an endothelial membrane glycoprotein involved in cardiovascular morphogenesis and vascular remodeling. It associates with transforming growth factor-? (TGF-?) signaling receptors to bind TGF-? family members, forming a functional receptor complex. Arterial injury leads to up-regulation of endoglin, but the underlying regulatory events are unknown. The transcription factor KLF6, an immediate-early response gene induced in endothelial cells during vascular injury, transactivates TGF-?, TGF-? signaling receptors, and TGF-?-stimulated genes. KLF6 and, subsequently, endoglin were colocalized to vascular endothelium (ie, expressed in the same cell type) following carotid balloon injury in rats. After endothelial denudation, KLF6 was induced and translocated to the nucleus; this was followed 6 hours later by increased endoglin expression. Transient overexpression of KLF6, but not Egr-1, stimulated endogenous endoglin mRNA and transactivated the endoglin promoter. This transactivation was dependent on a GC-rich tract required for basal activity of the endoglin promoter driven by the related GC box binding protein, Sp1. In cells lacking Sp1 and KLF6, transfected KLF6 and Sp1 cooperatively transactivated the endoglin promoter and those of collagen alpha1(I), urokinase-type plasminogen activator, TGF-?1, and TGF-? receptor type 1. Direct physical interaction between Sp1 and KLF6 was documented by coimmunoprecipitation, pull-down experiments, and the GAL4 one-hybrid system, mapping the KLF6 interaction to the C-terminal domain of Sp1. These data provide evidence that injury-induced KLF6 and preexisting Sp1 may cooperate in regulating the expression of endoglin and related members of the TGF-? signaling complex in vascular repair.
0006-4971
4001-4010
Botella, Luisa M.
33922361-7216-4770-8b71-fc2369e7df06
Sánchez-Elsner, Tilman
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Sanz-Rodriguez, Francisco
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Kojima, Soichi
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Shimada, Jun
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Guerrero-Esteo, Mercedes
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Cooreman, Michael P.
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Ratziu, Vlad
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Langa, Carmen
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Vary, Calvin P.H.
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Ramírez, Jose R.
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Friedman, Scott
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Bernabéu, Carmelo
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Botella, Luisa M.
33922361-7216-4770-8b71-fc2369e7df06
Sánchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Sanz-Rodriguez, Francisco
4a9d2acd-9f91-47e4-b836-21a1b21d1243
Kojima, Soichi
c536a179-307e-4324-b058-a5b6b259dfc1
Shimada, Jun
f1bef5f6-5fab-46c7-967a-1a9caeb20746
Guerrero-Esteo, Mercedes
03689efc-c91e-42c8-96d8-7bddc204dafd
Cooreman, Michael P.
d735f324-c4d8-4551-a665-059dab6f3a0d
Ratziu, Vlad
47004a8d-5746-4665-8cd4-1523de6ba6b6
Langa, Carmen
0de1f831-149d-42f6-b792-cb66d3d6b6e9
Vary, Calvin P.H.
f05b6deb-9452-4147-9fe4-b9a323434ba5
Ramírez, Jose R.
6243dd72-2431-4ff4-8622-a276f1f174e6
Friedman, Scott
4f203ee9-0a69-4ebb-a27b-52431f881945
Bernabéu, Carmelo
30da3b6d-c832-4d23-8ea8-79e4c808ca05

Botella, Luisa M., Sánchez-Elsner, Tilman, Sanz-Rodriguez, Francisco, Kojima, Soichi, Shimada, Jun, Guerrero-Esteo, Mercedes, Cooreman, Michael P., Ratziu, Vlad, Langa, Carmen, Vary, Calvin P.H., Ramírez, Jose R., Friedman, Scott and Bernabéu, Carmelo (2002) Transcriptional activation of endoglin and transforming growth factor-? signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury. Blood, 100 (12), 4001-4010. (doi:10.1182/blood.V100.12.4001).

Record type: Article

Abstract

Endoglin is an endothelial membrane glycoprotein involved in cardiovascular morphogenesis and vascular remodeling. It associates with transforming growth factor-? (TGF-?) signaling receptors to bind TGF-? family members, forming a functional receptor complex. Arterial injury leads to up-regulation of endoglin, but the underlying regulatory events are unknown. The transcription factor KLF6, an immediate-early response gene induced in endothelial cells during vascular injury, transactivates TGF-?, TGF-? signaling receptors, and TGF-?-stimulated genes. KLF6 and, subsequently, endoglin were colocalized to vascular endothelium (ie, expressed in the same cell type) following carotid balloon injury in rats. After endothelial denudation, KLF6 was induced and translocated to the nucleus; this was followed 6 hours later by increased endoglin expression. Transient overexpression of KLF6, but not Egr-1, stimulated endogenous endoglin mRNA and transactivated the endoglin promoter. This transactivation was dependent on a GC-rich tract required for basal activity of the endoglin promoter driven by the related GC box binding protein, Sp1. In cells lacking Sp1 and KLF6, transfected KLF6 and Sp1 cooperatively transactivated the endoglin promoter and those of collagen alpha1(I), urokinase-type plasminogen activator, TGF-?1, and TGF-? receptor type 1. Direct physical interaction between Sp1 and KLF6 was documented by coimmunoprecipitation, pull-down experiments, and the GAL4 one-hybrid system, mapping the KLF6 interaction to the C-terminal domain of Sp1. These data provide evidence that injury-induced KLF6 and preexisting Sp1 may cooperate in regulating the expression of endoglin and related members of the TGF-? signaling complex in vascular repair.

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Published date: December 2002

Identifiers

Local EPrints ID: 47979
URI: http://eprints.soton.ac.uk/id/eprint/47979
ISSN: 0006-4971
PURE UUID: 734c2121-3715-4e99-8c89-120396196093
ORCID for Tilman Sánchez-Elsner: ORCID iD orcid.org/0000-0003-1915-2410

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Date deposited: 16 Aug 2007
Last modified: 18 Feb 2021 17:09

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Contributors

Author: Luisa M. Botella
Author: Francisco Sanz-Rodriguez
Author: Soichi Kojima
Author: Jun Shimada
Author: Mercedes Guerrero-Esteo
Author: Michael P. Cooreman
Author: Vlad Ratziu
Author: Carmen Langa
Author: Calvin P.H. Vary
Author: Jose R. Ramírez
Author: Scott Friedman
Author: Carmelo Bernabéu

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