Navigation Links
Study sheds light on deadly lung disease
Date:4/14/2008

Systemic sclerosis (SSc), also known as scleroderma, is characterized by the formation of fibrosis, or scar tissue, on internal organs as well as the skin. Beyond its disfiguring symptoms, SSc is associated with a high rate of deadly lung disease. Pulmonary fibrosis strikes at least one-third of SSc sufferers, and kills 30 percent within 10 years. Assessing and treating SSc remains challenging, despite recent clinical trials, due in part to an incomplete understanding of the origins and progression of this autoimmune disorder.

To add to the understanding of SSc, particularly as it relates to lung fibrosis, researchers with the Royal Free and University College Medical School and Royal Brompton Hospital in London conducted experiments on a novel mouse model of scleroderma. Their results, published in the April 2008 issue of Arthritis & Rheumatism (www.interscience.wiley.com/journal/arthritis), provide insight into extreme vulnerability to fibrosis associated with injury to alveolar epithelial cells (AECs)cells that line the tiny air sacs in the lungsaggravated by the expression of a major immune-system player, transforming growth factor (TGF ).

Led by Dr. Christopher P. Denton, the researchers generated a transgenic mouse strain, which develops ubiquitous skin and sporadic lung scar tissuecharacteristics similar to humans with SSc and pulmonary fibrosis. They then set out to test their hypothesis that these transgenic mice would be more susceptible than wild-type mice to lung disease. To induce minor lung injury, a single dose of either saline or the antibiotic bleomycina widely accepted model of SSc skin fibrosiswas administered surgically to populations of both transgenic and wild-type mice. Representatives from each mouse strain were left untreated to serve as controls. After 3, 7, 10, 14, 21, 35, and 60 days, lung samples were dissected and preserved for biochemical, histological, and electron microscopic analysis.

Transgenic mice consistently demonstrated an exaggerated fibrosis-proliferation response to minor lung injury. The lungs from transgenic mice given normal, unbuffered saline demonstrated fibrotic traits similar to lungs from wild-type mice injected with fibrosis-inducing bleomycin, indicating a very low threshold for epithelial injury in the transgenic strain. Among other notable findings, electron microscopy revealed AEC abnormalities in the lungs of transgenic controls and bleomycin-affected wild-type mice; the lungs of transgenic mice given bleomycin showed severe epithelial damage. The level of collagen was elevated in the lungs from transgenic mice after doses of either bleomycin or saline. After injury with bleomycin, the lungs of transgenic mice demonstrated increased density of the TGF protein, implicated in the formation of fibrosis as well as tissue inflammation. Persistent fibrosis in transgenic mice injured with bleomycin was found independent of inflammation, but associated with impaired alveolar epithelial repair.

These results suggest that in the context of fibroblast-specific perturbation of TGF signaling, even minor epithelial injury induces significant fibrosis, Dr. Denton concludes. The model supports a central role for TGF in determining fibrosis and demonstrates that lung fibroblasts may regulate the response of AECs to injury.

Despite its limitations, including the fact that animal models with targeted genetic manipulations cannot fully represent all the facets and factors in the associated human disease process, this novel mouse study contributes to the understanding of the pathogenesis of systemic sclerosis and pulmonary fibrosis. Whats more, it provides a valuable reference point and motivation for future studies into anti-fibrotic therapies.


'/>"/>

Contact: Sean Wagner
swagner@bos.blackwellpublishing.com
781-388-8550
Wiley-Blackwell
Source:Eurekalert

Related medicine news :

1. NovoCure presents results from breast cancer pilot study
2. Mayo-led study finds smoking related to subset of colorectal cancers
3. National hospice study reveals gaps in service
4. Study Points to New Treatments for Polycystic Kidney Disease
5. MRI better than MDCT in detecting endoleaks, study says
6. Personality study shows risk of first depression episode late in life
7. 3T MRI plays significant role in detecting prostate cancer, study says
8. Study shows doctors offices can help stem abuse of Oxycontin, other narcotic painkillers
9. Quintiles Ranks First in Pan-European Clinical Investigator Study
10. Study Showed Minimally Invasive Surgery Reduced Risk of Hospital-Acquired Infections Compared to Open Surgery
11. NEJM study demonstrates carotid stenting with embolic protection is comparable to surgery
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/9/2016)... ... 2016 , ... Groth Family Insurance, a Washington-based firm offering ... a charity drive to support the family of Cindy Hendrickson, a local mother ... On October 29th of this year, Cindy Hendrickson swerved to avoid an oncoming ...
(Date:12/9/2016)... Ohio (PRWEB) , ... December 09, 2016 , ... ... of miniature, folded, pharmaceutical inserts and outserts. As a means of expanding ... This addition will enable Flottman to individually code professional inserts (PIs) and patient ...
(Date:12/9/2016)... Yorktown Heights, NY (PRWEB) , ... December 09, 2016 , ... ... on Alcoholism and Drug Dependence, Inc. (NCADD) is recommending the film Whispering ... 29 states and the District of Columbia as an education tool in the war ...
(Date:12/9/2016)... (PRWEB) , ... December 09, 2016 , ... An inventor ... amputees to safely ride all types of amusement park rides. , The patent-pending SAFETY ... unit is easy to use and could be set up in a matter of ...
(Date:12/9/2016)... ... December 09, 2016 , ... ... Pierre Hotel in New York, NY, on December 3rd, to benefit Holy Name ... attended the annual event, which raised over $1 million - the largest event ...
Breaking Medicine News(10 mins):
(Date:12/9/2016)... Japan , Dec. 9, 2016 Mitsubishi ... ; President & Representative Director, CEO: Dr. Masayuki ... amyotrophic lateral sclerosis (ALS) given edaravone intravenously in 10-14 ... loss as measured by the ALS Functional Rating Scale-Revised ... International Symposium on ALS/MND in Dublin, ...
(Date:12/9/2016)... DUBLIN , Dec 9, 2016 Research ... Vaccines Market 2016-2020" report to their offering. ... The global travel vaccines market ... The report covers the present scenario and the growth ... the market size, the report considers the revenue generated from the ...
(Date:12/9/2016)... Dec. 9, 2016  Forge Therapeutics, Inc. today ... Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) to advance ... the treatment of bacterial infections including those caused ... as an attractive antibacterial target for more than ... suitable chemical starting points has hampered its progress. ...
Breaking Medicine Technology: