New study reveals potential treatment benefits

Philadelphia, October 11, 2022 – Colon dysmotility, especially problems associated with constipation and diarrhea, is common in adults and children and can have a significant impact on quality of life.a new research in American Journal of Pathologypublished by Elsevier identified neuropilin 2 (NRP2) as a novel regulator of distal colonic smooth muscle motility. Its ability to modulate cytoskeletal tone and inhibit abnormal contractions of smooth muscle provides an opportunity in the future to inhibit or activate signaling and thereby modulate smooth muscle activity in patients suffering from colonic motility disorders. there’s a possibility that.

“Normal visceral smooth muscle activity is central to the function of many body systems, including the gastrointestinal and urinary tracts, but is less studied than vascular smooth muscle,” said co-principal investigator Maryrose P. Sullivan, Department of Surgery. The doctor explained. Harvard Medical School; and Department of Urology, Boston Healthcare System, Virginia, Boston, Massachusetts, USA. “Previous studies by our group showing strong expression of Nrp2 in colonic smooth muscle led us to understand the functional importance of Nrp2 in colonic contraction and motility.”

The researchers found widespread NRP2 expression in the distal colon in both human and mouse models, particularly in circular and longitudinal smooth muscle. They used genetically modified mice to examine the effect of Nrp2 deletion on colonic contractility. They demonstrated widespread expression of Nrp2 in smooth muscle of the gastrointestinal tract and determined its functional impact on the gastrointestinal tract. Nrp2 gene deletion in vitro Motility analysis of intact mice. Their findings showed that in mice with global or smooth muscle-specific deletion of Nrp2, colon tissue showed increased evoked contractions. Mice lacking inducible smooth muscle-specific Nrp2 also showed increased colonic motility.

“We were intrigued by the functional changes that appeared as early as 1 week after deletion of Nrp2,” said co-principal investigator Rosalyn M. Dr. Adam said. Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA. “The relatively rapid detection of differences in the contractile behavior of colonic muscles does not argue against major structural changes in the tissue, but rather suggests changes in cell signaling, which is regulated by Nrp2 in smooth muscle. Delineating the signaling networks involved is a major focus of our ongoing research.”

Dr. Sullivan and Dr. Adam say their work provides important additional information in understanding the regulatory mechanisms of visceral smooth muscle and raises the possibility that Nrp2 may be a practical target in diseases characterized by abnormal smooth muscle contraction. It was observed that this suggests that there is a gender.

“While studies in patients are many years away, ongoing research in our group is focused on developing small molecule inhibitors designed to inhibit Nrp2. These efforts may provide an opportunity in the future to inhibit Nrp2-mediated signaling and modulate smooth muscle activity in patients, which may be particularly relevant in diseases in which visceral smooth muscle is impaired. “This is because no effective drug therapy for these diseases is currently available,” the researchers noted.

Changes in colon motility can be caused by a variety of conditions, including birth defects such as Hirschsprung’s disease, diabetes, inflammation, infections, dysbiosis, and nerve damage secondary to spinal cord injury. . Additionally, changes in the magnitude and/or coordination of contractile activity throughout the gastrointestinal tract can lead to dysmotility with impaired intestinal flora, inflammation, and nutrient absorption, often leading to serious health consequences. brings.