The digestive system's smooth muscle tone is maintained by a molecular pathway, a study has found.
Researchers from the University of Massachusetts (UMass) Medical School have found a new molecular pathway that keeps the smooth muscles of the digestive system in check. The calcium ion-controlled pathway found in their mice study may aid in the development of treatments for a range of digestive diseases including incontinence, swallowing disorders, gastroesophageal reflux (GERD) and pancreatitis.
Senior author and associate professor of microbiology and physiological systems Ronghua ZhuGe said that the study underpins genetic studies involved in treating digestive disorders.
Understanding the molecular pathway of the digestive system is crucial in the development of treatment options that target specific genes. Available treatments for diseases such as reflux are not without side effects. For instance, a past study has shown that those who take proton-pump inhibitors have a 20 to 50 percent chance of developing chronic kidney disease.
According to a 2012 study, gastrointestinal disorders are a substantial source of morbidity, mortality and cost in the United States, with GERD as the most common diagnosis in more than 8 million visits.
"Knowing how these muscles stay contracted for such long periods of time will allow us to develop potential new treatments for these diseases," said ZhuGe. "The next step is to see whether this molecular mechanism in mice also operates in humans."
To keep the sphincters functioning well, these must often be in their basal tone. Smooth muscles maintain their basal tone by remaining contracted for long periods of time. Having healthy functioning sphincters is important in the digestive system. When the sphincters become impaired, serious diseases like achalasia or GERD can occur.
To gain insight on how smooth muscles can stay contracted for a long time, the team studied the internal anal sphincter of mice. They found that genetic deletion of a calcium-dependent MLC kinase (MLCK) eliminates basal tone and makes mice become incontinent. To further understand the pathway, ZhuGe and colleagues sought the help of Misheng Zhu from Nanjing University in China to produce mice that would allow them to switch off channels and test their hypothesis. Switching off the calcium ion-controlled pathway or TMEM16A indeed cause the mice to lose most of its basal tone.
The study findings were published in Nature Communications.
Photo: Rene Schwietzke | Flickr
