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Scientists Discover Link Between Protein, Lung Disease

September 16, 2009

In a development that could lead to a novel approach to the treatment of a devastating lung disease, biochemists at The University of Texas Health Science Center at Houston report they are the first to link the osteopontin (OPN) protein to chronic obstructive pulmonary disease (COPD). Findings appear online and will be in the January 2010 print issue of The FASEB Journal, the journal of The Federation of American Societies for Experimental Biology.

More than 12 million Americans are currently diagnosed with this incurable illness, which is the fourth leading cause of death, the National Heart Lung and Blood Institute reports. In the United States, the term COPD includes two main conditions – emphysema and chronic obstructive bronchitis.

The researchers were able to prevent COPD features in a mouse model by genetically removing osteopontin. To gauge the applicability of their findings to humans, the investigators analyzed the airways of people with COPD and found elevated levels of the protein.

“This is an important crossover study,” said Michael Blackburn, Ph.D., the study’s senior author and professor in the Department of Biochemistry and Molecular Biology at The University of Texas Medical School at Houston. “Because we can show osteopontin is elevated in people with COPD, this suggests that osteopontin could serve as both an indicator of disease progression and a therapeutic target.”

In the study, researchers induced COPD features in mice and then compared symptoms experienced by mice with osteopontin and those without. The mice without the protein had less inflammation and lung disease. “The lack of osteopontin in the mice prevented the COPD features,” said Daniel Schneider, the study’s lead author and an M.D./Ph.D. candidate at the UT Health Science Center at Houston.

“This paper reveals exciting new information on the pathogenetic mechanisms involved in the development of chronic obstructive pulmonary disease and emphysema,” said Richard J. Castriotta, M.D., professor and director of the Pulmonary, Critical Care and Sleep Medicine Division at the UT Medical School at Houston and medical director of the Sleep Disorder Center at Memorial Hermann – Texas Medical Center.

The study stems from research in Blackburn’s laboratory involving a signaling molecule named adenosine, which can orchestrate the process of inflammation in wound healing. Adenosine can also activate a cell surface receptor associated with COPD named A2B and produce osteopontin.

Blackburn’s decade-long research has focused on blocking the A2B receptor. With the new study linking osteopontin to COPD, Blackburn believes his laboratory may have uncovered a protein that could lead to a more targeted approach to treating emphysema.

“As a physician scientist, one goal of drug development is to offer more specific drug targets to treat the disorder and osteopontin provides a specific target that may be associated with fewer side effects,” Schneider said.

“This paper adds a new element, osteopontin, to the mix by discovering its significant role in the development of COPD with emphysema … It’s still too early to be used clinically, but there may be a place for osteopontin in the future as an indicator of lung disease in progress that leads to COPD and emphysema,” Castriotta said.

Blackburn is director of the Graduate Program in Biochemistry and Molecular Biology at the UT Medical School.

Schneider is a graduate research assistant at The University of Texas Graduate School of Biomedical Sciences at Houston and is a recipient of a T32 training grant by the Center for Clinical and Translational Sciences at the UT Health Science Center at Houston.

The study is titled “Adenosine and osteopontin contribute to the development of chronic obstructive pulmonary disease.” Other contributors from the Department of Biochemistry and Molecular Biology were graduate students Janci C. Lindsay and Yang Zhou, as well as senior research assistant Jose G. Molina.

The study was funded by the National Institutes of Health and the National Center for Research Resources.

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