A new protein discovered at Boston University School of Medicine (BUSM) in the laboratory of Nader Rahimi, PhD, may change the way patients with chronic kidney disease are treated. In Dr. Rahimi’s laboratory, a team of researchers discovered transmembrane and immunoglobulin containing 1 (TMIGD1) in renal epithelial cells. This protein was found to have a protective effect on the cells, suggesting that increasing expression of TMIGD1 in cells affected by chronic kidney disease may be an effective treatment option that addresses the drawbacks of current treatments.
“While dialysis and transplantation are considered the cornerstone of therapy for both forms of renal failure, none of these strategies directly targets the kidney proximal epithelial cells,” said study co-author Vipul Chitalia, MD, PhD, in a news release. “Therapeutic agents that could protect these cells from death can prevent and retard renal damage, thus postponing dialysis or need for transplantation.”
The paper, “TMIGD1 Is a Novel Adhesion Molecule That Protects Epithelial Cells from Oxidative Cell Injury,” was published in The American Journal of Pathology. Together, Emad Arafa and Dr. Philip A. Bondzie, along with colleagues at BUSM, conducted a set of experiments that identified the structure of TMIGD1 and elucidated the function of the protein in renal epithelial cells. The results showed that TMIGD1 can regulate the electrical current flowing through renal cells and the permeability of the cells. It further controls activities such as cell migration and cell morphology.
Most important to a strategy exploiting TMIGD1 as a potential target for therapy, TMIGD1 protects renal cells from injury caused by nutrient deprivation and oxidative damage. When the research team depleted TMIGD1 in renal cells and applied hydrogen peroxide to the cells, there was significant cell death. However, when they increased TMIGD1, they saw a protective effect.
“This study demonstrates that by altering the function of TMIGD1, it is possible to reduce kidney epithelial cell death and possibly avoid the high incidence of kidney failure and morbidity associated with kidney injury,” said Dr. Rahimi. A variety of options may be available to exploit these new findings. For example, researchers could try to increase the expression of TMIGD1 in renal cells by delivering mRNA for the protein or by delivering siRNA or a small molecule inhibitor targeted against negative regulators of the protein. Future tests are thus required.