1180
M. Eberlein et al
Inhibition of CTGF expression by statins
IGARASHI, A., NASHIRO, K., KIKUCHI, K., SATO, S., IHN, H.,
FUJIMOTO, M., GROTENDORST, G.R. & TAKEHARA, K. (1996).
Connective tissue growth factor gene expression in tissue sections
from localized scleroderma, keloid, and other ®brotic skin
disorders. J. Invest. Dermatol., 106, 729 ± 733.
MURPHY, M., GODSON, C., CANNON, S., KATO, S., MACKENZIE,
H.S., MARTIN, F. & BRADY, H.R. (1999). Suppression subtractive
hybridization identi®es high glucose levels as a stimulus for
expression of connective tissue growth factor and other genes in
human mesangial cells. J. Biol. Chem., 274, 5830 ± 5834.
ILLINGWORTH, D.R., ERKELENS, D.W., KELLER, U., THOMPSON,
G.R. & TIKKANEN, M.J. (1994). De®ned daily doses in relation to
hypolipidaemic ecacy of lovastatin, pravastatin, and simvasta-
tin. The Lancet, 343, 1554 ± 1555.
MULLER, G.A., FRANK, J., RODEMANN, H.P. & ENGLER-BLUM, G.
(1995). Human renal ®broblast cell lines (tFKIF and tNKF) are
new tools to investigate pathophysiologic mechanisms of renal
interstitial ®brosis. Exp. Nephrol., 3, 127 ± 133.
ITO, Y., ATEN, J., BENDE, R.J., OEMAR, B.S., RABELINK, T.J.,
WEENING, J.J. & GOLDSCHMEDING, R. (1998). Expression of
connective tissue growth factor in human renal ®brosis. Kidney
Int., 53, 853 ± 861.
JAKOBISIAK, M., BRUNO, S., SKIERSKI, J.S. & DARZYNKIEWICZ, Z.
(1991). Cell cycle-speci®c eects of lovastatin. Proc. Natl. Acad.
Sci. U.S.A., 88, 3628 ± 3632.
JOHNSON, D.W., SAUNDERS, H.J., FIELD, M.J. & POLLOCK, C.A.
(1999). In vitro eects of simvastatin on tubulointerstitial cells in
a human model of cyclosporin nephrotoxicity. Am. J. Physiol.,
276, F467 ± F475.
KEANE, W.F. (2000). The role of lipids in renal disease: Future
challenges. Kidney Int., 57, 27 ± 31.
NEGRE-AMINOU, P., VAN VLIET, A.K., VAN ERCK, M., VAN THIEL,
G.C., VAN LEEUWEN, R.E. & COHEN, L.H. (1997). Inhibition of
proliferation of human smooth muscle cells by various HMG-
CoA reductase inhibitors; comparison with other human cell
types. Biochim. Biophys. Acta., 1345, 259 ± 268.
OEMAR, B.S., WERNER, A., GARNIER, J.M., DO, D.D., GODOY, N.,
NAUCK, M., MARZ, W., RUPP, J., PECH, M. & LUSCHER, T.F.
(1997). Human connective tissue growth factor is expressed in
advanced atherosclerotic lesions. Circulation, 95, 831 ± 839.
PARK, Y.S., GUIJARRO, C., KIM, Y., MASSY, Z.A., KASISKE, B.L.,
KEANE, W.F. & O'DONNELL, M.P. (1998). Lovastatin reduces
glomerular macrophage in¯ux and expression of monocyte
chemoattractant protein-1 mRNA in nephrotic rats. Am. J.
Kidney Dis., 31, 190 ± 194.
KIM, S.I., HAN, D.C.
& LEE, H.B. (2000). Lovastatin inhibits
transforming growth factor-beta 1 expression in diabetic rat
glomeruli and cultured rat mesangial cells. J. Am. Soc. Nephrol.,
11, 80 ± 87.
PEREIRA, R.C., DURANT, D. & CANALIS, E. (2000). Transcriptional
regulation of connective tissue growth factor by cortisol in
osteoblasts. Am. J. Physiol Endocrinol. Metab., 279, E570 ± E576.
KIM, S.-Y., GUIJARRO, C., O'DONNELL, M.P., KASISKE, B.L., KIM,
Y. & KEANE, W.F. (1995). Human mesangial cell production of
monocyte chemoattractant protein-1: Modulation by lovastatin.
Kidney Int., 48, 363 ± 371.
PIEK, E., HELDIN, C.-H. & TEN DIJKE, P. (1999). Speci®city,
diversity, and regulation in TGF-beta superfamily signaling.
FASEB J., 13, 2105 ± 2124.
POMERANTZ, K.B., LANDER, H.M., SUMMERS, B., ROBISHAW, J.D.,
KOCH, G., BENZ, C., SCHMIDT, G., OLENIK, C. & AKTORIES, K.
(1997). Role of Rho proteins in lovastatin-induced breakdown of
actin cytoskeleton. J. Pharmacol. Exp. Ther., 283, 901 ± 909.
KOTHAPALLI, D., FRAZIER, K.S., WELPLY, A., SEGARINI, P.R. &
GROTENDORST, G.R. (1997). Transforming growth factor beta
induces anchorage-independent growth of NRK ®broblasts via a
connective tissue growth factor- dependent signaling pathway.
Cell Growth Dier., 8, 61 ± 68.
BALCUEVA, E. & HAJJAR, D.P. (1997). Gprotein-mediated
signaling in cholesterol-enriched arterial smooth muscle cells. 1.
Reduced membrane-associated G-protein content due to dimin-
ished isoprenylation of G-gamma subunits and p21ras. Biochem-
istry, 36, 9253 ± 9531.
RIESSEN, R., AXEL, D.I., FENCHEL, M., HERZOG, U.U., ROSSMANN,
& KARSCH, K.R. (1999). Eect of HMG-CoA reductase
H.
inhibitors on extracellular matrix expression in human vascular
smooth muscle cells. Basic. Res. Cardiol., 94, 322 ± 332.
ROSENBLOOM, J., SAITTA, B., GAIDAROVA, S., SANDORFI, N.,
ROSENBLOOM, J.C., ABRAMS, W.R., HAMILTON, A.D., SEBTI,
S.M., KUCICH, U. & JIMENEZ, S.A. (2000). Inhibition of type I
collagen gene expression in normal and systemic sclerosis
®broblasts by a speci®c inhibitor of geranylgeranyl transferase
I. Arthritis Rheum., 43, 1624 ± 1632.
KUCICH, U., ROSENBLOOM, J.C., SHEN, G., ABRAMS, W.R.,
HAMILTON, A.D., SEBTI, S.M.
& ROSENBLOOM, J. (2000).
TGF-beta1 stimulation of ®bronectin transcription in cultured
human lung ®broblasts requires active geranylgeranyl transferase
I, phosphatidylcholine-speci®c phospholipase C, protein kinase
C-delta, and p38, but not erk1/erk2. Arch. Biochem. Biophys.,
374, 313 ± 324.
LAU, L.F.
&
LAM, S.C. (1999). The CCN family of angiogenic
STROEBEL, M. & GOPPELT-STRUEBE, M. (1994). Signal transduc-
tion pathways responsible for serotonin-mediated prostaglandin
G/H synthase expression in rat mesangial cells. J. Biol. Chem.,
269, 22952 ± 22957.
VAN AELST, L. & D'SOUZA-SCHOREY, C. (1997). Rho GTPases and
signaling networks. Genes Dev., 11, 2295 ± 2322.
regulators: the integrin connection. Exp. Cell Res., 248, 44 ± 57.
LAUFS, U., ENDRES, M., CUSTODIS, F., GERTZ, K., NICKENIG, G.,
LIAO, J.K. & BOHM, M. (2000). Suppression of endothelial nitric
oxide production after withdrawal of statin treatment is mediated
by negative feedback regulation of rho GTPase gene transcrip-
tion. Circulation, 102, 3104 ± 3110.
VRTOVSNIK, F., COUETTE, S., PRIE, D., LALLEMAND, D.
&
LERNER, E.C., HAMILTON, A.D. & SEBTI, S.M. (1997). Inhibition of
Ras prenylation: a signaling target for novel anti-cancer drug
design. Anticancer Drug Des., 12, 229 ± 238.
MARON, D.J., FAZIO, S. & LINTON, M.F. (2000). Current perspectives
on statins. Circulation, 101, 207 ± 213.
MASON, R., LI, X.J. & WAHAB, N.A. (1997). High glucose induces the
expression of connective tissue growth factor in human mesangial
cells. J. Am. Soc. Nephrol., 8, 642A.
MASSY, Z.A., KIM, Y., GUIJARRO, C., KASISKE, B.L., KEANE, W.F. &
O'DONNELL, M.P. (2000). Low-density lipoprotein-induced
expression of interleukin-6, a marker of human mesangial cell
in¯ammation: eects of oxidation and modulation by lovastatin.
Biochem. Biophys. Res. Commun., 267, 536 ± 540.
FRIEDLANDER, G. (1997). Lovastatin-induced inhibition of
renal epithelial tubular cell proliferation involves a p21ras
activated, AP-1-dependent pathway. Kidney Int., 52, 1016 ± 1027.
VRTOVSNIK, F., ESSIG, M., IIMURA, O. & FRIEDLANDER, G. (1999).
Eect of lipid-lowering strategies on tubular cell biology. Kidney
Int. Suppl., 71, S92 ± S96.
WASSMANN, S., LAUFS, U., BAUMER, A.T., MULLER, K., KONKOL,
C., SAUER, H., BOHM, M. & NICKENIG, G. (2001). Inhibition of
Geranylgeranylation Reduces Angiotensin II-Mediated Free
Radical Production in Vascular Smooth Muscle Cells: Involve-
ment of Angiotensin AT1 Receptor Expression and Rac1
GTPase. Mol. Pharmacol., 59, 646 ± 654.
ZANG, F.L. & CASEY, P.J. (1996). Protein prenylation: Molecular
mechanisms and functional consequences. Annu. Rev. Biochem.,
65, 241 ± 269.
MULLER, G.A., SCHETTLER, V., MULLER, C.A. & STRUTZ, F. (1996).
Prevention of progression of renal ®brosis: how far are we?
Kidney Int. Suppl., 54, S75 ± S82.
(Received March 16, 2001
Revised May 3, 2001
Accepted May 16, 2001)
British Journal of Pharmacology vol 133 (7)