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Defective signaling pathway sheds light on cystic fibrosis
Date:2/14/2010

In a study that could lead to new therapeutic targets for patients with the cystic fibrosis, a research team from the University of California, San Diego School of Medicine has identified a defective signaling pathway that contributes to disease severity. In the study, published in the journal Nature Medicine, the researchers report that defective signaling for a protein called the peroxisome proliferator-activated receptor-γ (PPAR-γ) accounts for a portion of disease symptoms in cystic fibrosis, and that correction of the defective pathway reduces symptoms of the disease in mice.

In the paper published in the February 14 edition of the journal, lead investigator Gregory Harmon, MD, study supervisor Christopher Glass, MD, PhD, professor of cellular and molecular medicine, and colleagues show that both mice and cells from patients with cystic fibrosis have a defect in signaling for PPAR-γ, as a result of reduced levels of prostaglandins that activate the receptor.

Cystic fibrosis is the most common, potentially lethal genetic disease among whites, occurring in one in 3,000 births. The disease is a multisystem condition that leads to progressive lung failure, pancreatic failure and gastrointestinal obstruction, or blockage.

"Cystic fibrosis results from a genetic mutation in a channel, or membrane pore, that facilitates the transport of chloride and bicarbonate electrolytes from inside the cell to the spaces outside the cell," said Harmon. "Loss of the cystic fibrosis pore channel results in inflammation and mucus accumulation. It also results in dehydration of the cell surfaces that make up the lining spaces inside the lungs and other affected organs, such as the intestinal tract."

Exactly how the process occurs has been a matter of intense scientific scrutiny; yet despite numerous therapeutic advances, individuals with the disease continue to endure a shortened lifespan. "Someone born in the 1990s wit
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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