Markey study shows nutrient-regulated hormone alters stem cell function

LEXINGTON, Ky. (October 6, 2021) New study from the lab of University of Kentucky cancer director Mark Evers, MD, demonstrates the essential role of the hormone neurotensin in cell proliferation and stem cell function in the small intestine.

Recently published in Cellular and Molecular Gastroenterology and Hepatology, the study highlights two different functions of the small peptide hormone neurotensin (NT) in the small intestine, where function depends on the availability of nutrients. The significant results of this study expand knowledge about gut hormones and how NT performs different functions depending on nutrient availability.

The study aimed to determine a novel role for NT in intestinal stem cells (ISCs). SAIs are responsible for maintaining the cell pool of the intestines, which makes them essential for proper absorption of nutrients. Complete turnover of intestinal epithelial cells occurs every four to five days, making the regulation of ICS vital. These cells have the ability to become more specialized cells, contributing to the normal functioning of the intestines. The team of researchers demonstrated the essential role of NT in the regulation of ISC using a combination of in vivo and in vitro models.

The main results of the study define the new role of NT on intestinal cells defined by two different nutrient states:

  • During nutrient abundance, NT activates pathways to aid cell proliferation.
  • During nutrient deprivation, the peptide hormone uses other pathways to preserve ISC function.

These two roles are essential for maintaining normal physiological function, but also demonstrate the critical importance of regulated NT signaling.

“Our study shows that NT function undergoes a change during fasting,” said Stephanie Rock, Ph.D., a recent graduate of the Department of Cancer Toxicology and Biology’s doctoral program and lead author of the study. . “In the fed state, NT primarily regulates the proliferation of intestinal cells, but during fasting, we have found that NT plays a critical role in maintaining the function of ICSs, which are essential for the proper functioning of the liver. small intestine. “

“Our research group reported over 20 years ago that exogenous administration of NT could stimulate growth of the intestinal lining, however, the exact mechanisms were not known,” Evers said. “Our current study indicates that NT has a strong effect on gut stem cells and that this effect is different depending on nutritional status, highlighting the new role of NT in energy balance and maintenance of a normal intestinal mucosa. ”

This study was funded by R01 DK112034 (BME), R01 CA208343 (BME and TG), R01 CA133429 (TG), and R35 GM131807 (JJ) grants from the National Institutes of Health. BME is supported by the Markey Cancer Foundation. SR was supported by an NIH T32 Training Grant DK007778. The research used the following Shared Resource Facilities (SRF), supported by National Cancer Institute (BME) grant P30 CA177558: Biospecimen Procurement and Translational Pathology SRF, Biostatistics and Bioinformatics SRF, Flow Cytometry and Immune Monitoring SRF, and Oncogenomics Shared Resource Facilities. The content is the sole responsibility of the authors and does not necessarily represent the official opinions of the National Institutes of Health.

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