WEDNESDAY, March 12 (HealthScoutNews) -- In one of the more complicated biomedical research stories you will encounter this year, scientists at the University of California at San Francisco have identified a gene that can increase susceptibility to the cr

Dr. David G. Morris, an assistant professor of medicine at the university and leader of the group reporting the finding in the March 13 issue of Nature, can explain it all to you in about 10 minutes, if you are willing to follow a tangled tale of genes, enzymes and proteins. And although the research was done with mice, it might lead to better treatment of emphysema in humans. The gene in question is one whose activity affects growth factor-beta (TGF-beta), which is already known to be involved in one lung disease, fibrosis, that involves the growth of unwanted tissue in the lungs. Emphysema is a completely different condition, in which there is slow degradation of lung tissue, specifically the alveoli, the tiny air sacs through which oxygen flows. The alveoli become abnormally enlarged and lose elasticity because of the steady destruction of a vital structural protein, elastin. Emphysema is known to be caused by smoking. However, genetics also plays a role, because most people who smoke for decades do not develop the disease -- only 10 percent to 15 percent do. One genetic defect has already been identified, an absence of alpha-1 antitrypsin, which protects against the destruction of elastin. What Morris has identified is a gene that is involved in both fibrosis and emphysema and whose activity affects the role of a pivotal enzyme called transforming growth factor-beta in a way that had not been imagined. "TGF-beta has always been thought of as a fibrosis cytokine," Morris says. "This is a new way of looking at TGF-beta -- that its absence leads to emphysema." It works this way. The gene makes a section of one protein in a family called integrins, which are found on the surface of cells. One form of TGF-beta can bind to that protein and start a chain of molecular events that leads to excess production of tissue by overactivity of another form of TGF-beta, causing fibrosis. When that section is deleted, fibrosis is prevented. However, Morris now says that aging mice lacking that form of the integrin also develop emphysema because there is steady destruction of lung tissue caused by the inactivation of TGF-beta. That demonstration has not been easy, he adds, because until now, mice missing the gene for that segment of the integrin died shortly after birth. The work "opens doors to trying to understand emphysema in humans, why some people get it where others don't," Morris says. A human study has already begun. Researchers at Harvard Medical School have assembled a cohort of patients and families in whom emphysema occurs early in life without an alpha-1 antitrypsin defect. "This opens a whole series of things that people can look at," says Anita B. Roberts, chief of the laboratory of cell regulation and carcinogenesis at the National Cancer Institute, who wrote an accompanying editorial in the journal. The work, she adds, is "confusing but exciting." "Whether this happens in humans has not been shown yet, but now there is whole set of candidate genes that they can look at," Roberts says.

<< Prev	CIGoutlet.NET News Home	Next >>