Scientists at the University of Texas at Dallas have made a remarkable discovery, revealing a previously unknown “housekeeping” process in kidney cells that contributes to their rejuvenation and sustained health. This self-renewal mechanism, which differs from the regeneration processes observed in other bodily tissues, sheds light on how the kidneys can remain healthy throughout a person’s lifetime. The findings of this study were published in Nature Nanotechnology on April 17.

Unlike organs like the liver and skin, where cells divide to generate new cells for regeneration, the cells in the proximal tubules of the kidney exhibit mitotic quiescence. This means they do not actively divide to create new cells. While kidney cells possess limited repair capabilities in cases of mild injury or disease, and stem cells can generate new kidney cells to some extent, severe injury or chronic disease often leads to cell death without the possibility of regeneration. Overcoming this challenge is crucial in managing kidney diseases, as current treatments can only slow down the progression of kidney failure but cannot effectively repair the organ.

The newly discovered self-renewal mechanism represents a significant breakthrough in understanding kidney health. Dr. Jie Zheng, a Distinguished Chair in Natural Sciences and Mathematics at the University of Texas at Dallas, expressed the importance of this finding. He highlighted the potential for advancements in nanomedicine and early detection of kidney disease resulting from further research in this field.

The unexpected discovery emerged during the investigation of gold nanoparticles’ filtration through the kidneys and their clearance through urine. While it was known that gold nanoparticles pass through the kidney’s glomerulus and accumulate in the proximal tubules, the precise mechanism of their escape from the tubular cells remained unclear.

During their study, the research team utilized electron microscopes to examine gold nanoparticles in proximal tubular tissue samples. To their surprise, they observed vesicles containing nanoparticles and organelles outside the cells. These vesicles contained lysosomes, mitochondria, endoplasmic reticulum, and other cell components that are typically confined within cells. The contents of these outwardly facing bulges in the luminal membranes of the tubular cells were then pinched off into vesicles and released into the extracellular space.

This newly identified extrusion-mediated self-renewal mechanism is fundamentally different from other regenerative processes and housecleaning tasks observed in cells. Unlike processes like exocytosis, which involve the fusion of vesicle membranes with the cell’s membrane to release contents, this mechanism involves the direct extrusion of cellular contents without membrane fusion. This unique process allows cells to eliminate old materials, update themselves with fresh contents, and ensure longer survival and proper functionality.

The researchers believe that their findings open up new avenues for exploration. Understanding how nanoparticles are eliminated from the proximal tubules is crucial in the field of nanomedicine to minimize their accumulation in the body. Additionally, investigating how to regulate or monitor this self-renewal process could lead to advancements in maintaining kidney health in patients with conditions like high blood pressure or diabetes. Noninvasive detection of the process’s signature could potentially serve as an indicator of early-stage kidney disease.

The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Science Foundation, and the Cancer Prevention and Research Institute of Texas.