Annual Fall Meeting of GBM Abstracts Symposia Authors Contact

Bettina Krüger, Susanne Mühlich, Thomas Huff, Angela Graness, Margarete Goppelt-
Strübe
Alterations in the actin and microtubular network influence
CTGF expression in endothelial cells
CTGF (connective tissue growth factor) is widely recognized as a fibrogenic factor, but
was originally described as a protein released from serum-stimulated endothelial cells. It
mediates adherence and migration of monocytes, vascular smooth muscle cells, and
activated platelets suggesting a functional role in the development of atherosclerotic
lesions and plaque rupture. Shear stress was shown to induce CTGF suggesting that
changes in cell morphology and alterations of the cytoskeleton influence CTGF
expression.
CTGF expression was investigated in primary cultures of HUVEC and in a glomerular
microvascular endothelial cell line. Treatment of these cells with colchicine disassembled
the microtubular network, which resulted in RhoA activation and stress fibre formation
accompanied by a dramatic up-regulation of CTGF. Inhibition of the RhoA-associated
Kinase (ROCK) by Y27632 prevented stress fibre formation and CTGF expression,
indicative of a role for RhoA in both processes. Disassembly of F-actin by latrunculin B,
which increases G-actin levels, decreased CTGF expression suggesting a reverse
relationship between them. This was supported by incubation of endothelial cells with
thymosin beta 4, which induced CTGF expression by sequestering G-actin, or by
yasplakinolide, which reduced G-actin levels by stabilization of F-actin.
Disruption of microtubules by colchicine was also accompanied by a fragmentation of the
golgi apparatus. A comparable staining pattern was also observed, when the cells were
treated with brefeldin A, which directly disrupts golgi transport. However, brefeldin A did
not induce CTGF mRNA and de novo biosynthesis. Taken together our data are in line
with the hypothesis that CTGF expression is related to G-actin levels, thereby linking
CTGF expression and morphological changes of endothelial cells.
contact:
Dr. Bettina Krüger
Universität Erlangen-Nürnberg
Nephrologie
bettina.krueger@fd42.de
Loschgestr. 8
91054 Erlangen (Deutschland)