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:3/24/2017)... ... 2017 , ... “End Time GPS”: a dauntless and enlightened study of ... GPS” is the creation of published author, Wesley Gerboth, a World War II veteran, ... space-vehicle projects. Now, at age ninety-one, he shares the Wisdom God bestowed upon him ...
(Date:3/24/2017)... ... March 24, 2017 , ... “The Adventures of Joey, The Dog Who ... who lives his life to the fullest, as God intended. “The Adventures of Joey, ... a mother and grandmother pursuing her passion for writing, especially about truth and human ...
(Date:3/23/2017)... ... March 23, 2017 , ... The physicians of KSF Orthopaedic ... greater Houston Area. The new location is located at 2255 E. Mossy Oaks Rd., ... Village. This newest location will provide patients living in the north Houston area (The ...
(Date:3/23/2017)... Montclair, NJ (PRWEB) , ... March 23, 2017 ... ... the Renaissance Oklahoma City Convention Center at 10 North Broadway Avenue, will be ... 6.0 hours of relevant, practical instruction in the management of chronic pain. , ...
(Date:3/23/2017)... , ... March 23, 2017 , ... 82% of adults are unaware of the dangers ... not brush their teeth the minimum two times a day that dentists recommend. The ramifications ... 51 million hours of school and adults missing 164 million hours of work each year ...
Breaking Medicine News(10 mins):
(Date:3/23/2017)... , March 23, 2017 The key ... population, increasing diabetic population, accelerating economic growth and increasing healthcare ... industry are higher life expectancy of ESRD patients, rising demand ... markets. However, the expansion of the market is hindered by ... ...
(Date:3/23/2017)... , March 23, 2017  Transportation Insight, a ... an end-to-end supply chain management firm with expertise serving ... Product Solutions Rick Zaffarano was named a ... the Supply Chain by the only publication exclusively dedicated ... food supply chain. "Rick has brought to ...
(Date:3/23/2017)... INDIANAPOLIS , March 23, 2017  Eli ... the William Sansum Diabetes Center have established a research ... by diabetes through enhanced research, education and care. ... disease bears a disproportionate weight on Latino families in ... David Kerr , M.D., FRCPE, director of Innovation and ...
Breaking Medicine Technology: