New research from the University of Illinois Chicago has found that heparanase, HPSE, a poorly understood protein, is a key regulator of cells’ innate defence mechanisms.
So what exactly is an innate defence mechanism?
As the name suggests, these are cellular mechanisms that are triggered by various danger signals. They have been conserved in many species throughout evolution. It can set such a system in action against pathogens like viruses, etc and also by environmental toxins, and dysfunctional cells which possibly accumulate.
A further deep study on these processes can give more insight to generate multi-target therapy against a variety of human diseases.
Led by Alex Agelidis, a UIC MD/Ph.D. dual degree medical student, and Dr Deepak Shukla, the UIC Marion Schenk Professor of Ophthalmology and UIC professor of microbiology and immunology at the College of Medicine, the team used a systems approach to track shifts in important cellular building blocks in cells and mice genetically engineered to lack HPSE.
The team showed HPSE acts as a cellular crossroads between antiviral immunity, proliferative signals, and cell death.
Agelidis explained that we have known the HPSE to drive late-stage inflammatory diseases, although it was once thought this was primarily because of enzymatic activity of the protein breaking down heparan sulfate, a sugar molecule present in chains on the surface of virtually all cells.
While a major focus of the study was on identifying mechanisms of pathogenesis of herpes simplex virus (HSV-1), their work has broad implications to treat diseases involving dysregulation of HPSE, including cancer, atherosclerosis and autoimmune disorders.
Alex Agelidis, Benjamin A. Turturice, Rahul K. Suryawanshi, Tejabhiram Yadavalli, Dinesh Jaishankar, Joshua Ames, James Hopkins, Lulia Koujah, Chandrashekhar D. Patil, Satvik R. Hadigal, Evan J. Kyzar, Anaamika Campeau, Jacob M. Wozniak, David J. Gonzalez, Israel Vlodavsky, Jin-ping Li, David L. Perkins, Patricia W. Finn, Deepak Shukla. Disruption of innate defense responses by endoglycosidase HPSE promotes cell survival. JCI Insight, 2021; DOI: 10.1172/jci.insight.144255