Featured Research

from universities, journals, and other organizations

Study Sheds Light On Deadly Lung Disease

Date:
April 17, 2008
Source:
Wiley-Blackwell
Summary:
Systemic sclerosis, 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.

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.

Related Articles


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, provide insight into extreme vulnerability to fibrosis associated with injury to alveolar epithelial cells (AECs)—cells that line the tiny air sacs in the lungs—aggravated by the expression of a major immune-system player, transforming growth factor β (TGF β).

Led by Dr. Christopher P. Denton, the researchers generated a transgenic mouse strain, which develops ubiquitous skin and sporadic lung scar tissue—characteristics 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 bleomycin—a widely accepted model of SSc skin fibrosis—was 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 β 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 β signaling, even minor epithelial injury induces significant fibrosis,” Dr. Denton concludes. “The model supports a central role for TGF β 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. What’s more, it provides a valuable reference point and motivation for future studies into anti-fibrotic therapies.


Story Source:

The above story is based on materials provided by Wiley-Blackwell. Note: Materials may be edited for content and length.


Cite This Page:

Wiley-Blackwell. "Study Sheds Light On Deadly Lung Disease." ScienceDaily. ScienceDaily, 17 April 2008. <www.sciencedaily.com/releases/2008/04/080414155241.htm>.
Wiley-Blackwell. (2008, April 17). Study Sheds Light On Deadly Lung Disease. ScienceDaily. Retrieved April 25, 2015 from www.sciencedaily.com/releases/2008/04/080414155241.htm
Wiley-Blackwell. "Study Sheds Light On Deadly Lung Disease." ScienceDaily. www.sciencedaily.com/releases/2008/04/080414155241.htm (accessed April 25, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, April 25, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

85 Killed in Niger by Meningitis Since Start of Year

85 Killed in Niger by Meningitis Since Start of Year

AFP (Apr. 24, 2015) A meningitis outbreak in Niger has killed 85 people since the start of the year prompting authorities to close schools in the capital Niamey until Monday. Video provided by AFP
Powered by NewsLook.com
C-Section Births a Trend in Brazil

C-Section Births a Trend in Brazil

AFP (Apr. 24, 2015) More than half of Brazil&apos;s babies are born via cesarean section, as mothers and doctors opt for a faster and less painful experience despite the health risks. Duration: 02:02 Video provided by AFP
Powered by NewsLook.com
Anti-Malaria Jab Hope

Anti-Malaria Jab Hope

Reuters - News Video Online (Apr. 24, 2015) The world&apos;s first anti-malaria vaccine could get the go-ahead for use in Africa from October if approved by international regulators. Paul Chapman reports. Video provided by Reuters
Powered by NewsLook.com
3D Food Printing: The Meal of the Future?

3D Food Printing: The Meal of the Future?

AP (Apr. 23, 2015) Developers of 3D food printing hope the culinary technology will revolutionize the way we cook and eat. (April 23) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins