• Press Release

Mount Sinai Study Uncovers Mechanisms of Reactive Oxygen Species in Stem Cell Function and Inflammation Prevention

Findings could improve prevention and treatment of inflammatory bowel diseases

  • New York, NY
  • (October 03, 2022)

Mount Sinai researchers have published one of the first studies to demonstrate the importance of reactive oxygen species in maintaining stem cell function and preventing inflammation during wound repair, which could provide greater insights into the prevention and treatment of inflammatory bowel diseases (IBD), according to findings published in the journal Gut on October 3.

Reactive oxygen species are highly reactive chemicals formed from oxygen. They serve as prime signals of cellular dysfunction that contribute to diseases. Secretion of reactive oxygen species in the intestine is necessary for maintaining stem cell function and important for wound repair; however, it can cause inflammatory effects as well. The Mount Sinai team found the key transcription factors driving abnormal stem cell changes, suggesting a significant role of reactive oxygen species in maintaining healthy intestines.

“While it’s clear that regulation of oxygen and reactive oxygen species plays a critical role in chronic diseases generally, and IBD in particular, this study provides a major advance in defining the key role of oxygen species in maintaining a healthy epithelial barrier for IBD,” said senior author Judy H. Cho, MD, Dean for Translational Genetics and Ward-Coleman Chair in Translational Genetics, and Vice Chair of Pathology, Molecular and Cell-Based Medicine at the Icahn School of Medicine at Mount Sinai.

The research team studied the role of reactive oxygen species and NOX1, the protein used to produce these chemicals, by examining single-cell gene expression in vitro and in vivo in mice models, as well as ex vivo in the form of human intestinal biopsies obtained following routine colonoscopies. They measured the amount of reactive oxygen species and analyzed the gene expression profile of intestine barrier cells from mice and human patients with a subtype of IBD known as ulcerative colitis. Intestine barrier cells cover the intestine surface and help to digest food, absorb nutrients, and prevent the invasion of gut bacteria. The Mount Sinai researchers compared gene expression data in both inflamed and uninflamed colon tissues.

The researchers found that a combination of NOX1, loss of function—which results in decreased reactive oxygen species, plus the presence of a substance known as TNF that causes inflammation leads to an abnormal increase of microfold cells. Microfold cells, also known as M cells, are crucial to regulating gut immune response. The research team found this abnormal increase in M cells in stem cells, in both the human and mice models, as a result of loss of reactive oxygen species. This increase in epithelial M cells drives increased recruitment of immune cells in mice. By treating intestine cells with reactive oxygen species, they were able to reverse the initial defect caused by losing reactive oxygen species during inflammation.

“Reactive oxygen specifies released by stem cells are critical in maintaining a heathy gut via maintaining proper balance of intestine barrier cell types,” said lead author Nai-Yun Hsu, PhD, Associate Scientist in the Judy Cho Laboratory. The researchers encourage further studies, which they said could include direct reactive oxygen species-stem cell modulation therapy to IBD patients in future treatments. 

The University of Oxford in Oxford, United Kingdom, contributed to the research. The study was supported by funding from the National Institutes of Health and the Sanford J. Grossman Charitable Trust.


About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2023-2024.

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