COLUMBIA, Mo. –When the immune system is activated, certain receptors that work as “switches” turn on processes that help the body fight pathogens that cause disease. If these receptors “stay on” after the body has protected itself, the immune system may begin to attack healthy parts of the body. In a new study, University of Missouri researchers have determined that a type of P2 nucleotide receptors, known as a P2Y2 receptor, plays a role in Sjögren’s syndrome, a predominately female disease affecting 4 million Americans. Sjögren’s syndrome is believed to be caused by immune cells attacking and destroying the exocrine glands that produce tears and saliva. Understanding how the P2Y2 receptor interacts with the immune system could lead to novel targets for therapeutic strategies for Sjögren’s syndrome, including engineering salivary gland tissue.
“There is no known cure for Sjögren’s syndrome; patients with the syndrome experience a decrease in their quality of life with few treatment options,” said Gary Weisman, professor in the Department of Biochemistry and investigator in the Christopher S. Bond Life Sciences Center. “Although designed to help us, the immune system is the cause of a lot of our grief when it is over-activated. P2Y2 receptors are known to be activated in damaged or diseased salivary glands and may play a role in tissue repair. They can be either the good guy or the bad guy depending on the cell type in which they are located.”
P2 receptors are present in nearly all cells and tissues where they mediate diverse functions, including muscle contraction, neurotransmission, insulin secretion, wound healing and cell growth. Previous studies have indicated that P2Y2 receptors may have a role in several diseases, including cystic fibrosis, cardiovascular disease, Parkinson’s disease and Alzheimer’s disease.
“The diversity of cellular responses mediated by P2Y2 receptors is due in part to unique structural features,” said Jean Camden, a researcher in the Department of Biochemistry. “P2Y2 receptors are activated by nucleotides released near the site of damage.”
Previously, MU researchers isolated the human P2Y2 receptor gene and expressed the receptor in a cell model that normally lacks the receptor. These studies eventually led researchers to find that the receptor plays a role in both salivary gland regeneration and the inflammatory response associated with Sjögren’s syndrome.
Their most recent study, “P2Y2 Nucleotide Receptors Mediate Metalloprotease-dependent Phosphorylation of Epidermal Growth Factor Receptor and ErbB3 in Human Salivary Gland Cells,” was published in the Journal of Biological Chemistry and describes how these receptors may promote salivary gland regeneration.
 The Department of Biological Engineering is part of the College of Engineering and College of Agriculture, Food and Natural Resources
Kelsey Jackson, JacksonKN@missouri.edu, (573) 882-8353