Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

SERPINE2 identified as novel candidate gene for COPD, especially with smoking

04.04.2005


Major tissue, cell protease inhibitor’s role in lung previously unrecognized



Using a combination of genetic linkage, microarray gene expression and genetic association studies, a group of Brigham and Women’s Hospital/ Harvard Medical School researchers have identified a serine protease inhibitor clade E, member 2, or SERPINE2, "as a novel candidate susceptibility gene for COPD," according to Sorachai Srisuma, who is presenting the research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005.

The collaborative, multi-disciplinary team includes: Sorachai Srisuma, Dawn L. DeMeo, Brigham H. Mecham, Edwin K. Silverman, Scott T. Weiss, Kathleen J. Haley, John J. Reilly, Steven D. Shapiro, and Thomas J. Mariani. Mariani, head of the lab where Srisuma works, said the gene is "the most promising susceptibility candidate due to its biological relevance, its expression correlation with disease characteristics, and the allelic association in COPD families and replication in non-familial COPD patients."


*Paper presentation: "Expression of Serine Proteinase Inhibitor E2, a novel candidate COPD susceptibility gene, in the lung," 12:30 p.m.-3 p.m. Tuesday April 5, Physiology 936.4/board #A490. On view 7:30 a.m. - 4 p.m.

Feature topic presentation: Srisuma also is participating in featured topic session #477, "Receptors and signaling pathways in lung injury and repair," Sunday April 3 room 30A. It begins at 3:15 p.m. Srisuma’s presentation is scheduled for 4:15 p.m.

First major study to seek SERPINE2’s physiological role in lung

Srisuma said SERPINE2 "was of particular interest due to its pattern of expression and relationship to alpha-1-antitypsin, the only gene proven to modify risk to COPD (chronic obstructive pulmonary disease). Our team of human genetic epidemiologists, led by Dawn DeMeo and Edwin Silverman, previously identified a region on chromosome 2 they thought might contain a gene conferring susceptibility to COPD.

"We used DNA chips, or gene expression microarrays, to identify genes within this region that were expressed in the lung," Srisuma noted. "Subsequently we showed that specific cells in the lungs express SERPINE2, and that its expression is altered in individuals with certain clinical characteristics of COPD. Furthermore, specific forms of the gene, termed polymorphisms or SNPs, were more common in people who developed COPD," he said. Taken together, "these data strongly suggest SERPINE2 is a gene capable of modifying COPD risk, particularly in response to smoking," he added.

SERPINE2 is a major tissue and cell-associated inhibitor of thrombin and plasmin, but not elastase, Srisuma noted. But no significant study of this protease inhibitor’s expression in normal or diseased lungs had been undertaken previously. "In an effort to begin to gain insight into the physiological role of SERPINE2 in the lung, we investigated the temporal and spatial expression pattern of the gene in mouse and human lungs," he said.

Analysis of two independent microarray data sets describing normal mouse lung development revealed prominent SERPINE2 expression, which was maximal during formation of the airspaces, which is related to lung maturation. Immunostaining was performed to identify the location of SERPINE2 within the lung.

SERPINE2 shows analogous pattern in diseased human, normal mouse lungs

Prominent immunolocalization of SERPINE2 was observed in a cell-associated pattern within bronchiolar airway epithelial cells and in an extracellular matrix-associated pattern in the vascular adventitia. Immunohistochemistry in human lungs demonstrated an analogous staining pattern. "Our studies revealed cell-specific and developmentally-regulated expression of SERPINE2 in the lung, which supports further investigation of this gene’s role in human lung diseases," Srisuma said.

Next steps. Already the group has characterized where and when SERPINE2 is expressed in the lung at various developmental stages. "We are also investigating the specific role of SERPINE2 mutations in lung function and the risk of developing COPD in humans and genetically modified animals," Srisuma noted. "We hope this line of investigation will show how SERPINE2 affects the risk of developing COPD and how smoking contributes to this process," he added.

In the future, Srisuma will pursue a project identifying potential biomarkers in COPD patients from New England and also in his native Thailand. When he completes his current post-doctoral fellowship and returns home, a collaborative study will proceed related to lung development and pathogenesis of COPD and pediatric lung diseases.

Funding. This and related research are supported by the National Institutes of Health.

Scope of the problem, hope for behavior change

About 16 million Americans suffer from COPD, a chronic inflammatory disorder characterized by a gradual loss of lung function. Strongly associated with cigarette smoking, COPD is the only disease among the top 10 causes of death in the U.S. with an increasing rate of newly diagnosed cases. Already the fourth leading cause of death in the U.S., some believe it could be the leading cause of death worldwide by 2010. So far, there is no cure for COPD, and doctors can only relieve symptoms.

Similar to diseases like cancer and heart diseases, people who smoke (or breathe second-hand smoke) have an increased risk of developing COPD, including emphysema and chronic bronchitis. Certain individuals are more susceptible than others, in that they have an increased risk of developing disease in response to smoking. For instance, people with a rare form of the protein made by the gene alpha-1-antitrypsin have a high risk of developing COPD if they smoke. Individuals with the common form of this protein have a low risk of developing emphysema, but increase their chances of getting disease if they smoke.

Srisuma said that nearly all individuals are thought to have other genes that contribute to their risk of developing COPD. Researchers have previously identified some candidate susceptibility genes and further studies may help identify people with increased risk of disease. "The identification of individuals with increased risk would be beneficial," he said, "if they can modify their smoking behavior. Further research also may hasten the detection diseased individuals, which will be especially useful if it also leads to potential therapies," Srisuma added.

Mayer Resnick | EurekAlert!
Further information:
http://www.the-aps.org
http://www.iups2005.org/

More articles from Life Sciences:

nachricht Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg

nachricht Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Polymers Based on Boron?

18.01.2018 | Life Sciences

Bioengineered soft microfibers improve T-cell production

18.01.2018 | Life Sciences

World’s oldest known oxygen oasis discovered

18.01.2018 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>