UIC: the protein receptor in endothelial cells promotes healing in the lungs


In the blood vessels of the lungs, endothelial cells form a protective barrier that regulates how fluids and other substances, such as white blood cells, are transported in and out of lung tissue by the bloodstream. However, in some cases, the endothelium becomes more permeable – it becomes “permeable,” which leads to increased inflammation and fluid build-up in the lungs, a condition known as pulmonary edema. These are classic signs of respiratory conditions like Acute Respiratory Distress Syndrome, or ARDS, for which treatment options are limited both in number and in their ability to restore pulmonary vascular endothelial barrier function.

Now researchers at the University of Illinois at Chicago have identified a receptor expressed inside certain endothelial cells that, when activated, helps promote tissue regeneration and self-repair in models murine ARDS. Their findings are reported in Circulation Research, a journal of the American Heart Association.

“In our article, we described a population of endothelial cells in the lungs that express sphingosine phosphate 1 receptor 1 with the ability to repair endothelial integrity, which may prevent inflammatory pulmonary vascular injury,” Dolly said. Mehta, UIC Professor in the Department of Pharmacology and Regenerative Medicine at the College of Medicine and corresponding study author.

The sphingosine phosphate 1 receptor 1, or S1PR1, belongs to a family of receptors that associate with G proteins and play a role in the development and maintenance of blood vessels in several organs, including the lungs.

For the study, the researchers observed mice with lung leaks and mild inflammation.

First, they studied the generation of endothelial cells expressing the green fluorescent protein (GFP) -S1PR1 in mouse models. In these mice, any increase in GFP was indicative of S1PR1 activity. They also found that by activating certain cellular signals called transcription factors, they could increase the production of sphingosine 1 phosphate and help the cell generate more S1PR1 positive endothelial cells.

The researchers then studied the effects of the activated receptor in saving pulmonary vascular homeostasis. They injected endothelial cells expressing GFP-S1PR1 into mice with lung leaks and found that it reprogrammed endothelial cells by activating a self-healing signal. The mice that received the injection showed more signs of a healthy and selective endothelial barrier, such as reduced fluid accumulation.

“Our results show that culturing endothelial cells that express S1PR1 activates the endothelial regeneration program to mediate endothelial repair. These results raise the possibility of exploiting this pathway for potential drug treatments to restore vascular homeostasis in the states. of inflammatory vascular injury, ”Mehta said.

The co-authors of the study are Md-Zahid Akhter, Jagdish Joshi, Vijay Avin Balaji Ragunathrao, Mark Maienschein-Cline and Asrar Malik of UIC and Richard Proia of the National Institute of Diabetes and Digestive and Kidney Diseases.

This work was supported by grants from the National Institutes of Health (HL060678, HL137169, HL084153), the American Heart Association (19POST34450241), and the National Center for Advancing Translational Sciences (UL1TR002003).

This press release was produced by the University of Illinois at Chicago. The opinions expressed here are those of the author.

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