Top photo: Neuropilin 2 (Nrp2, green) is prominently distributed in longitudinal and circular colonic smooth muscle. The colocalization shown in the merged image indicates that Nrp2 is also expressed in Cajal’s stromal cells and is associated with type III receptor tyrosine kinase cancer biomarker (c-Kit), platelet-derived growth factor receptor Characterized by alpha (PDGFRa) positive cells and neural structures. Marked by synaptophysin. MYP, enteric plexus; CM, circular muscle; LM, longitudinal stripe (credit: Vivian Cristofaro and Maryrose Sullivan).
“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. . Furthermore, 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.
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Notes for editors
This article was published by George Lambrinos, Vivian Cristofaro, Kristine Pelton, Alexander Bigger-Allen, Claire Doyle, Evalynn Vasquez, Diane R. Bielenberg, Maryrose P. Sullivan, and Rosalyn M. It is a controlling factor.” .Adam (https://doi.org/10.1016/j.ajpath.2022.07.013(Opens in new tab/window)).will appear online in advance of American Journal of PathologyVolume 192, Issue 11 (November 2022), Publisher Elsevier.
Full text of the article is available to qualified journalists upon request. Contact Eileen Leahy on +1 732 238 3628 or [email protected](Opens in new tab/window) Request a PDF of the article. To request an interview with the author, please contact Boston Children’s Hospital’s Media Relations Group. [email protected](Opens in new tab/window)
about American Journal of Pathology
American Journal of Pathology(Opens in new tab/window)the official journal of American Society of Investigative Pathology(Opens in new tab/window)is published by Elsevier and seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors consider basic, translational, and clinical research that directly addresses mechanisms of pathogenesis or provides a foundation for future mechanistic studies. Examples of such fundamental research include data mining, biomarker identification, molecular pathology, and discovery research. High priority is given to the study of human diseases and related experimental models using molecular, cellular, and biological approaches.