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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>