Nav: Home

When mucus can be key to treating colon and airway diseases

February 01, 2019

Cells produce mucins at a constant rate, and when exposed to an allergen or pathogen, they produce more mucin in a rapid burst. Both the constant and rapid mucin secretion is controlled by calcium. CRG researchers Gerard Cantero-Recasens and Vivek Malhotra wanted to understand how normal cells secrete mucins in the right quantity and quality, so they can design procedures to correct mucin secretion defects in diseases where either too much or too little mucin is produced, such as asthma, chronic obstructive pulmonary disease, Crohn's disease and colorectal cancer.

Their data published in the journals eLife and Journal of Biological Chemistry, reveal two proteins called TRPM4 and NCX that work together to control mucin secretion both in healthy cells, and in cells derived from patients with cystic fibrosis. They have also identified a third protein called KChIP3 that senses calcium levels within healthy cells to release mucins, which is crucial to maintain the correct thickness of the mucous layer in the colon. This means cells possess means to control how much mucin they produce depending on the cellular needs. They can produce large amounts if an allergen or pathogen is present, or release it constantly to preserve the mucous layer.

"First, we carried out a genome wide screen which identified 25 proteins involved in mucin secretion in colon cancer cells," explains postdoctoral researcher Cantero-Recasens. "We discovered that a group of these proteins reside on the surface of the cells to control calcium entry, which in turn controls rapid release of mucins. The team has also discovered a calcium sensor, KChIP3, inside cells that controls baseline mucin secretion, which is crucial to maintain the correct thickness of the mucous layer. If this intracellular calcium sensor is lost, it causes massive release of mucin from colonic cancer cells."

He continues: "We were surprised by this finding - we didn't expect that cells use different sources of calcium - from internal and external sources - to control mucin secretion. We also didn't expect to find that the KChIP3 sensor controlling baseline (basal) mucin secretion does it by acting like a 'brake' to prevent mucin release. Mice without the KChIP3 gene have a much thicker mucous layer in the colon. This means KChIP3 could be a new target for drugs to control diseases with higher or lower levels of mucins."

And by studying different cell types, the team discovered the process cells use to control stimulated mucin secretion is the same in both the colon and the airways. "This is an exciting finding because it means targeting the molecules involved in mucin secretion process can be used to treat airway diseases such as asthma or chronic obstructive pulmonary disease (COPD), as well as the colon associated pathologies," explains Dr Cantero-Recasens.

ICREA research professor at the CRG, Vivek Malhotra and his group are now working with researchers at the Hospital Del Mar and IMIM to further test whether mucins and proteins involved in mucin secretion are genetically altered in patients with diseases of the airway and colon. They are also working to find chemical means to target functions controlled by proteins in mucin secretion pathway. Together, the genetic and chemical procedures to control mucin secretion could reveal new ways to detect and control progression of asthma, chronic obstructive pulmonary disease (COPD), irritable bowel disease and colorectal cancers.
-end-


Center for Genomic Regulation

Related Asthma Articles:

Insomnia prevalent in patients with asthma
A team of researchers from the University of Pittsburgh has found that insomnia is highly prevalent in adults with asthma and is also associated with worse asthma control, depression and anxiety symptoms and other quality of life and health issues.
Test used to diagnose asthma may not be accurate
A new study urges caution in the use of the mannitol challenge test for asthma in non-clinical settings.
Turning off asthma attacks
Working with human immune cells in the laboratory, Johns Hopkins researchers report they have identified a critical cellular 'off' switch for the inflammatory immune response that contributes to lung-constricting asthma attacks.
Access to asthma meds, plus flu vaccines, keep kids with asthma healthy
Kids need flu shots to prevent asthma flares, and medications available in school to keep 86 percent in class, according to two studies being presented at the American College of Allergy, Asthma and Immunology Annual Scientific Meeting.
Discovery could lead to better asthma treatment
Scientists have made a discovery that could lead to improved treatment for asthma sufferers.
Do asthma and COPD truly exist?
Defining a patient's symptoms using the historical diagnostic labels of asthma and chronic obstructive pulmonary disease (COPD) is an outdated approach to understanding an individual's condition, according to experts writing in the European Respiratory Journal today.
Asthma in many adolescents is not an allergic disease
New research indicates that asthma in many adolescents is not likely to involve inflammation of the airways and therefore should not be considered an allergic disease.
First classification of severe asthma
Severe asthma can have a devastating effect on sufferers, affecting their ability to work or go to school and to lead normal lives.
Exploring 'clinical conundrum' of asthma-COPD overlap in nonsmokers with chronic asthma
Researchers may be closer to finding the mechanism responsible for loss of lung elastic recoil and airflow limitation in nonsmokers with chronic asthma.
Asthma app helps control asthma: Alerts allergists when sufferers need assistance
New study in Annals of Allergy, Asthma and Immunology shows how an app directly connecting an allergist and an asthma sufferer can provide necessary intervention when asthma isn't under control.

Related Asthma Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".