Actin-dependent regulation of connective tissue growth factor

S. Muehlich, I. Cicha, C.D. Garlichs, B. Krueger, G. Posern, M. Goppelt-Struebe, American Journal of Physiology-Cell Physiology 292 (2007) C1732–C1738.

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Journal Article | English
Author
Muehlich, Susanne; Cicha, Iwona; Garlichs, Christoph D.; Krueger, BettinaLibreCat ; Posern, Guido; Goppelt-Struebe, Margarete
Abstract
Expression of connective tissue growth factor (CTGF) in endothelial cells is modulated by shear stress affecting the organization of the cytoskeleton. The molecular connection between alterations of actin and CTGF expression was investigated in human umbilical vein endothelial cells (HUVEC) and a microvascular endothelial cell line. Overexpression of nonpolymerizable monomeric actin R62D interfered with stress fiber formation in HUVEC and concomitantly reduced immunoreactive CTGF. In microvascular endothelial cells, flow-dependent upregulation of CTGF was prevented by this actin mutant. In contrast, overexpression of actin S14C strengthened filamentous actin and increased CTGF expression. These data indicated an inverse relationship between CTGF expression and monomeric actin. Coexpression of the mutant actins and different CTGF promoter constructs revealed an actin-sensitive site between 3 and 4.5 kb of the CTGF promoter. A CArG-like box at -3791 bp was responsible for actin-dependent CTGF induction as shown by mutagenesis. Overexpression of actin S14C activated the nonmutated promoter significantly more strongly than the mutated promoter. Actin polymerization is regulated by the small GTPase RhoA and activation of serum response factor (SRF). Overexpression of constitutively active RhoA or SRF significantly increased CTGF protein synthesis. The 4.5-kb promoter construct, but not the construct with a mutation in the CArG box, was activated by SRF or RhoA, providing evidence for a functional role of this site in CTGF induction. These findings provide novel evidence that monomeric actin is the connecting link between alterations in the cytoskeleton and CTGF gene expression and demonstrate the importance of SRF in regulating CTGF transcription.
Publishing Year
Journal Title
American Journal of Physiology-Cell Physiology
Volume
292
Issue
5
Page
C1732–C1738
LibreCat-ID

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Muehlich S, Cicha I, Garlichs CD, Krueger B, Posern G, Goppelt-Struebe M. Actin-dependent regulation of connective tissue growth factor. American Journal of Physiology-Cell Physiology. 2007;292(5):C1732–C1738. doi:10.1152/ajpcell.00552.2006
Muehlich, S., Cicha, I., Garlichs, C. D., Krueger, B., Posern, G., & Goppelt-Struebe, M. (2007). Actin-dependent regulation of connective tissue growth factor. American Journal of Physiology-Cell Physiology, 292(5), C1732–C1738. https://doi.org/10.1152/ajpcell.00552.2006
@article{Muehlich_Cicha_Garlichs_Krueger_Posern_Goppelt-Struebe_2007, title={Actin-dependent regulation of connective tissue growth factor}, volume={292}, DOI={10.1152/ajpcell.00552.2006}, number={5}, journal={American Journal of Physiology-Cell Physiology}, publisher={American Physiological Society}, author={Muehlich, Susanne and Cicha, Iwona and Garlichs, Christoph D. and Krueger, Bettina and Posern, Guido and Goppelt-Struebe, Margarete}, year={2007}, pages={C1732–C1738} }
Muehlich, Susanne, Iwona Cicha, Christoph D. Garlichs, Bettina Krueger, Guido Posern, and Margarete Goppelt-Struebe. “Actin-Dependent Regulation of Connective Tissue Growth Factor.” American Journal of Physiology-Cell Physiology 292, no. 5 (2007): C1732–C1738. https://doi.org/10.1152/ajpcell.00552.2006.
S. Muehlich, I. Cicha, C. D. Garlichs, B. Krueger, G. Posern, and M. Goppelt-Struebe, “Actin-dependent regulation of connective tissue growth factor,” American Journal of Physiology-Cell Physiology, vol. 292, no. 5, pp. C1732–C1738, 2007, doi: 10.1152/ajpcell.00552.2006.
Muehlich, Susanne, et al. “Actin-Dependent Regulation of Connective Tissue Growth Factor.” American Journal of Physiology-Cell Physiology, vol. 292, no. 5, American Physiological Society, 2007, pp. C1732–C1738, doi:10.1152/ajpcell.00552.2006.

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