Newswise — AUGUSTA, Ga. (May 9, 2023) – An extended RNA molecule plentifully present in sound smooth muscle cells, which provide our blood vessels with durability and suppleness, is also vital for the uninterrupted squeezing that propels food along our digestive system.
Devoid of CARMN, an extended, non-coding RNA, which implies that it does not generate proteins but aids in managing cell operations, the gastrointestinal tract, which spans 30 feet, does not contract as it ought to.
According to Jiliang Zhou, PhD, a vascular biologist in the Department of Pharmacology and Toxicology at the Medical College of Georgia, this can lead to a distressing and potentially fatal circumstance where incompletely digested food becomes trapped.
Zhou, who is the corresponding author of the study published in the journal Gastroenterology, remarks that "CARMN is a pivotal controller of contractility in both areas, and if it is not operating at its best, then neither are we."
In 2021, Zhou and his team disclosed in the journal Circulation that CARMN is the sole lengthy non-coding RNA that is persistently copious in human vascular smooth muscle cells within the blood vessels of both humans and mice. They also discovered that its existence is significantly reduced in vascular conditions such as atherosclerosis. Moreover, when they reinstated more usual levels in mice models with vascular disease, they noticed a notable reduction in scar formation and the unhealthy expansion of cells inside the blood vessels.
It was while conducting that research that the scientists became aware of CARMN's vital function in the propulsion of the gastrointestinal tract, which comprises our esophagus, stomach, and intestines.
Zhou observes that, in fact, CARMN seems to be more crucial in the GI tract than in the circulation of blood through our blood vessels since the heart's pulsation can propel blood.
Zhou emphasizes that "The aftermath of the malfunction of the contractility of smooth muscle cells in the GI tract would be far more severe than that in vascular smooth muscle cells. It is essential for their unceasing operation. You may take it for granted, but if it fails to do its job, you will encounter issues."
According to the MCG scientists, although it has been evident that difficulties with the propulsion of the GI tract can be problematic and even fatal, the specifics regarding what controls the smooth muscle cells that direct this crucial movement have been vague.
Zhou and his colleagues write that visceral smooth muscle cells are a fundamental component of the GI tract that is crucial to what is known as motility, or movement. This action is vital to the passage of food through the GI tract. Hindered movement can lead to different levels of intestinal pseudo-obstruction, where incompletely digested food accumulates in the intestines, causing bloating, abdominal pain, nausea, vomiting, and constipation or diarrhea, as per MedlinePlus. Additionally, the bladder, another hollow organ, may also be affected, which can impact the ability to urinate, as well as the uterus, which must generate potent contractions to facilitate childbirth.
While investigating their primary focus on vascular smooth muscle cells by completely eliminating CARMN to study the consequences, Zhou and his colleagues chanced upon this unforeseen function in the GI tract. They discovered that without CARMN, mice were unable to survive or experienced swollen bellies 100% of the time due to the insufficient contraction of the GI tract.
Zhou expresses that the finding was unanticipated. They discovered that the absence of CARMN caused the downregulation of multiple genes that support contractility, such as Mylk, which is a known key regulator of smooth muscle cell contraction. This deficiency also disrupted the communication and coordinated action of GI cells that enables them to function together "like an orchestra" to achieve coordinated movement. The same reactions were observed in both mouse models and human GI cells. Zhou also notes that the loss impeded their efforts to gain a better understanding of the long-term effects of modified CARMN levels in the vascular smooth muscle cells.
Based on their new discoveries, the researchers have recognized the necessity for a method to remove CARMN selectively. They are currently investigating options such as the CRISPR gene-editing tool in collaboration with Joe Miano, PhD, a genome editor and molecular biologist, as well as Benard Ogola, PhD, a pharmacologist, both from the MCG Vascular Biology Center. Additionally, they are looking into more straightforward techniques for enhancing CARMN levels, such as exercise.
The researchers are now interested in examining CARMN in the GI cells of individuals with intestinal pseudo-obstruction to determine whether its function has been altered by a mutation or if it has a lower expression.
Smooth muscle cells are distributed along the walls of the body's passages and hollow organs such as the GI tract and bladder. According to Zhou, CARMN is present only in smooth muscle cells, and the scientists were able to identify its exact location in animal models. He adds that there could be some variation in CARMN expression among individuals and in the specific location of smooth muscle cells. Furthermore, the expression of CARMN may change during pregnancy, such as in the uterus.
It seems that the scientists are planning to investigate the potential role of CARMN in aneurysms, but they have not yet started this work. However, based on their previous research, they have found that CARMN is distinctly diminished in vascular disease like atherosclerosis and that restoring more normal levels in mouse models of vascular disease can dramatically diminish scar formation and unhealthy cell proliferation inside the blood vessels.
In 2003, the Human Genome Project revealed that most of the RNA present in our genome, including CARMN, is noncoding RNA. However, noncoding RNA remains the least researched area of study to date.
The lead author of the study is Xiangqin He, PhD, a Postdoctoral Fellow who is supported by a postdoctoral fellowship from the American Heart Association. The research was funded by the National Heart, Lung and Blood Institute, as well as an Established Investigator Award and Transformational Project Award from the AHA to Zhou. Another coauthor, Kunzhe Dong, PhD, who was a Postdoc during the study and is now a faculty member at MCG's Immunology Center of Georgia, received a Career Development Award from the AHA.
Read the full study.
RSS