help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on January 27, 2005, doi:10.1165/rcmb.2004-0127OC

Am. J. Respir. Cell Mol. Biol., Volume 32, Number 4, April 2005, 290-300

A more recent version of this article appeared on April 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2004-0127OCv1
32/4/290    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Watts, K. L
Right arrow Articles by Spiteri, M. A
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watts, K. L
Right arrow Articles by Spiteri, M. A

Submitted on April 22, 2004
Revised on January 25, 2005

Simvastatin inhibits growth factor expression and modulates pro-fibrotic markers in lung fibroblasts

Keira L Watts1*, Edith M Sampson2, Gregory S Schultz2, and Monica A Spiteri1

1 Lung Research, Institute of Science and Technology in Medicine, University Hospital of North Staffordshire/ Keele University, Stoke on Trent, Staffordshire, United Kingdom, 2 Department of Obstetrics and Gynaecology, Institute of Wound Repair, Health Science Centre, University of Florida, Gainesville, Florida, USA

* To whom correspondence should be addressed. E-mail: keira_watts{at}yahoo.co.uk.

Simvastatin is best known for its antilipidaemic action and use in cardiovascular disease due to its inhibition of 3-hydroxy-3-methylglutaryl CoenzymeA (HMG CoA) reductase; a key enzyme in the cholesterol synthesis pathway. Inhibition of biological precursors in this pathway also enables pleiotrophic immunomodulatory and anti-inflammatory capabilities, including modulation of growth factor expression. Connective tissue growth factor (CTGF) and persistent myofibroblast formation are major determinants of the aggressive fibrotic disease, idiopathic pulmonary fibrosis (IPF). In this study we utilized human lung fibroblasts derived from healthy and IPF lungs to examine Simvastatin effects on CTGF gene and protein expression, analyzed by RT-PCR and ELISA respectively. Simvastatin significantly inhibited (p<0.05) CTGF gene and protein expression, overriding the induction by Transforming Growth Factor (TGF)-{beta}1, a known potent inducer of CTGF. Such Simvastatin suppressor action on growth factor interaction was reflected functionally on recognized phenotypes of fibrosis. {alpha}-SMA expression was downregulated and collagen gel contraction reduced by 4.94 and 7.58 fold in IMR90 and HIPF lung fibroblasts respectively when preconditioned with 10µM Simvastatin compared to TGF-{beta}1 treatment alone after 24 hours. Our data suggest that Simvastatin can modify critical determinants of the profibrogenic machinery responsible for the aggressive clinical profile of IPF, and potentially prevents adverse lung parenchymal remodeling associated with persistent myofibroblast formation.




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
A. N. C. Santana, R. A. Kairalla, and C. R. R. Carvalho
Potential Role of Statin Use in Idiopathic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., May 1, 2008; 177(9): 1048 - 1048.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. A. Black Jr. and P. C. Trackman
Transforming Growth Factor-{beta}1 (TGF{beta}1) Stimulates Connective Tissue Growth Factor (CCN2/CTGF) Expression in Human Gingival Fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent Mechanism: STATINS WITH FORSKOLIN BLOCK TGF{beta}1-INDUCED CCN2/CTGF EXPRESSION
J. Biol. Chem., April 18, 2008; 283(16): 10835 - 10847.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Shiroshita-Takeshita, B. J.J.M. Brundel, B. Burstein, T.-K. Leung, H. Mitamura, S. Ogawa, and S. Nattel
Effects of simvastatin on the development of the atrial fibrillation substrate in dogs with congestive heart failure
Cardiovasc Res, April 1, 2007; 74(1): 75 - 84.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
E Hothersall, C McSharry, and N C Thomson
Potential therapeutic role for statins in respiratory disease.
Thorax, August 1, 2006; 61(8): 729 - 734.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
C. K. Haston and T. J. Hudson
Finding Genetic Modifiers of Cystic Fibrosis
N. Engl. J. Med., October 6, 2005; 353(14): 1509 - 1511.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society.