Fibrosis is an all-too-common medical condition that globally is responsible for 800 million cases of chronic kidney disease and two million deaths from chronic liver diseases each year.
At present, little can be done to prevent fibrosis, which is caused by the excessive deposition of collagens and other structural proteins in the extracellular matrix — the glue-like material that keeps cells together and which facilitates wound healing.
In 2020, researchers at Vanderbilt University Medical Center reported that when FUS, a protein that stimulates collagen production, is blocked from entering the nucleus of kidney cells grown in culture, collagen levels drop.
Now they have found that levels of nuclear FUS are significantly increased in mouse models of injury-induced kidney and liver fibrosis and that less fibrosis occurs when a genetic mutation or cell-penetrating peptide blocks the transport of FUS into the nucleus.
Their report March 15 in the Journal of Clinical Investigation suggests that the peptide is “a promising therapeutic option for organ fibrosis,” the researchers concluded.
Manuel Chiusa, PhD, research assistant professor of Medicine, is the paper’s first author. Senior author is Ambra Pozzi, PhD, professor of Medicine and of Molecular Physiology and Biophysics and a senior research career scientist at the Nashville Veterans Affairs (VA) Medical Center.
Pozzi also holds the Thomas Golper Directorship at VUMC.
The peptide, a protein fragment called CP-FUS-NLS, was generated in collaboration with co-author Jacek Hawiger, MD, PhD, the Louise B. McGavock Distinguished Professor of Medicine at VUMC.
Other co-authors from VUMC are Youngmin Lee, MD, PhD, Ming-Zhi Zhang, MD, Raymond Harris, MD, Taylor Sherrill, Craig Brooks, PhD, Agnes Fogo, MD, Charles Flynn, PhD, Jozef Zienkiewicz, PhD, and Roy Zent, MD, PhD.
This work was supported in part by National Institutes of Health grants R01DK119212, R01DK069921, RF1AG064909, and R01DK056942, and by the U.S. Department of Veterans Affairs. Pozzi is the recipient of a VA Senior Research Career Scientist Award.