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:4/24/2017)... ... April 24, 2017 , ... My T Chai, a South African company ... available for purchase on RevNutrition.com, a popular website specializing in sales of nutritional products. ... in ancient India and Siam. It spread across Asia and Africa quickly, and today ...
(Date:4/24/2017)... HOUSTON, TEXAS (PRWEB) , ... April 24, 2017 ... ... service (SaaS) based healthcare compliance and credentialing solutions, today announced that Kyle Allain ... Allain leads symplr’s Cactus Provider Management sales and operations, including provider, payor and ...
(Date:4/24/2017)... ... April 24, 2017 , ... In 2017, up to ... approximately 25,000 of them will be malignant.(1) As research into precision medicine continues, ... healthcare model in the diagnosis and treatment of brain tumors. Healthcare facilities that ...
(Date:4/24/2017)... , ... April 24, 2017 , ... Rod Burkett, CEO ... Housing News website. , Rod has been at the forefront of Gardant since it ... As CEO, Rod has overseen the opening of more than 40 new senior living ...
(Date:4/24/2017)... ... ... As a former supermodel known for her timeless beauty, Joan Severance knows ... is that she put all the words in her new book, "Manifest Your Mate: ... and sparkling sense of humor have inspired her to write a book on how ...
Breaking Medicine News(10 mins):
(Date:4/19/2017)... DIEGO , April 19, 2017  Sorrento ... an antibody-centric, clinical-stage biopharmaceutical company developing new treatments ... announced the closing of its previously announced underwritten ... stock at a public offering price of $2.00 ... and estimated offering expenses payable by Sorrento.  The ...
(Date:4/19/2017)... 19, 2017  SARES•REGIS Group leased the first ... at Conejo Spectrum Business Park in ... Biotherapeutics, Inc. , a biopharmaceutical company developing meaningful ... that have been underserved by scientific innovation, with ... cancer, autoimmune and infectious disease. Before ...
(Date:4/18/2017)... Research and Markets has announced the addition ... their offering. ... devices market to grow at a CAGR of 6.35% during the ... 2017-2021, has been prepared based on an in-depth market analysis with ... its growth prospects over the coming years. The report also includes ...
Breaking Medicine Technology: