Navigation Links
Channeling efforts to fight cystic fibrosis
Date:9/17/2010

PHILADELPHIA - The lab of Kevin Foskett, PhD, the Isaac Ott Professor of Physiology at the University of Pennsylvania School of Medicine, has found a possible new target for fighting cystic fibrosis (CF) that could compensate for the lack of a functioning ion channel in affected CF-related cells. Their finding appears in the Journal of Clinical Investigation.

The team explored the role of CFTR, the chloride ion channel mutated in CF patients, in fluid secretion by mucous gland cells. They used a recently developed transgenic pig model, in which the CFTR gene has been knocked out. The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. The flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucous.

CF researchers had been held back because existing animal models did not fully mimic the problems seen in people with CF. In people, faulty mucous glands may contribute to airway dehydration and the problems associated with CF. Mucous glands found in the airways of the lung are important to breathing because they help clear inhaled irritants and bacteria. They are also the sites where important macromolecules critical for lung defense against pathogens are made.

CF is the most common genetic disease in the United States, affecting about 30,000 children and adults and about 70,000 worldwide. The CF mutation makes certain organs of the body susceptible to obstruction due to thick mucus secretions, especially in the lung where thick secretions lead to chronic infections. This requires a daily regimen of drugs and physical therapy to help clear airway secretions.

"We discovered, first, that the ion transport and signal transduction mechanisms in the pig cells appear to be precisely the same as those used in human cells, indicating that the pig is an excellent model for studies of human lung function and a valuable tool for elucidating pathology of lung disease in CF," notes Foskett.

The team also discovered that fluid secretion by the mucous cells -- in response to neurotransmitters -- requires CFTR. This secretion was absent in the pigs lacking CFTR. However, the same cells that lacked the CFTR chloride ion channel, mimicking the condition in human CF, expressed another, different chloride ion channel that could be activated by elevating intracellular calcium by the same neurotransmitters. The presence of both channels in the same mucous cells suggests that the calcium-activated chloride channel could be targeted therapeutically to compensate for lack of CFTR functioning channels in CF-harmed cells.

"This crosstalk between the signaling pathways that activate the two different chloride ion channels now gives us a completely new therapeutic strategy to think about," says Foskett. For example, the presence of the calcium-activated chloride channel would enable CF mucous cells to secrete in response to stimulation that would have normally required the CFTR channel. Drugs that could enhance the magnitude of the calcium response might also enable activation of calcium-activated chloride channel-mediated secretion in CF cells. Importantly, such agents might be able to lead to secretion only during times of physiological stimulus, utilizing the appropriate neural regulation of secretion that likely remains intact in CF.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. U-Ms efforts to encourage disclosure of medical errors decreased claims
2. Rhetoric, framing efforts have little influence in same-sex marriage debate
3. Drug control efforts in Mexico reduce methamphetamine treatment admissions in Mexico and US
4. Mayo Clinic researchers share latest findings in CT radiation dose reduction efforts
5. Leap forward in efforts to develop treatments for Huntingtons disease
6. New UN Entity Strengthens Global Efforts for Women & Girls
7. School-Based Efforts May Help Curb Obesity in High-Risk Kids
8. DeFreitas Gives to Haiti Relief Efforts
9. Huntington Beach Hotel and Resort Recognized for Elite Efforts to Conserve the Environment and Provide Guests with a Green Hotel Stay.
10. PMSI Advocacy Efforts Prompt CMS to Improve MSA Review Methodology
11. Protocol Q1 2010 Philanthropic Efforts a Resounding Success
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Channeling efforts to fight cystic fibrosis
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at The ... the most popular and least understood books in the Holy Scriptures, Revelation. The Book ... have baffled scholars for centuries. Many have tossed it off as mere rubbish, but ...
(Date:10/13/2017)... ... October 13, 2017 , ... “America On The Brink”: the Christian history ... The Brink” is the creation of published author, William Nowers. Captain Nowers and ... WWII veteran, he spent thirty years in the Navy. Following his career as ...
(Date:10/12/2017)... ... October 12, 2017 , ... The company has developed a ... and regulatory authorities worldwide. From Children’s to Adults 50+, every formula has been ... standard. , These products are also: Gluten Free, Non-GMO, Vegan, Soy Free, ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... drug delivery system that we intend to develop to enable prevention of a ... lead to severe hearing loss, especially in pediatric patients. For cisplatin, hearing loss ...
(Date:10/12/2017)... ... October 12, 2017 , ... On Saturday, October 21, the Health ... Miles by Moonlight to raise money for the American Heart Association Heart Walk. Teams ... Teams will work together to keep their treadmills moving for 5 hours. Treadmills will ...
Breaking Medicine News(10 mins):
(Date:9/18/2017)... , Sept. 18, 2017  PMD Healthcare of ... Pharmacy of Kalamazoo, Mich. , have ... service that expedites and streamlines patient and provider access ... 2.0, and wellness management services.  ... used to measure lung function for a variety of ...
(Date:9/12/2017)... , Sept. 12, 2017   EcoVadis , the leading platform ... published the first annual edition of its Global CSR Risk and Performance ... evaluated by EcoVadis, based on Scorecard Ratings that analyzed nearly 800,000 data ... ... ...
(Date:9/9/2017)... ... ... Monday, September 18 th .The Brain Tumor Foundation (BTF) begins a week-long ... BTF,s Mobile MRI Unit – a 70 Ft. ... brings its nationwide initiative, the Road to Early Detection Sponsor-A-City Campaign to ...
Breaking Medicine Technology: