A team of researchers from the University of Texas at Dallas has unveiled a previously undisclosed “housekeeping” process within kidney cells. This process expels unwanted materials, enabling the cells to rejuvenate themselves and maintain their functionality and vitality. This distinctive self-renewal mechanism, unlike known regeneration processes observed in other bodily tissues, sheds light on how the kidneys can sustain their well-being over a person’s lifetime, even in the absence of injury or illness. The team has published their groundbreaking findings in a recent study featured in Nature Nanotechnology.
In contrast to organs like the liver and skin, where cells divide to generate new offspring and regenerate the organ, kidney cells in the proximal tubules exhibit mitotic quiescence—they do not divide to create new cells. While kidney cells do possess limited repair capabilities in cases of mild injury or disease, and kidney stem cells can generate new kidney cells up to a certain point, severe injuries or chronic diseases typically result in cell death without the ability to regenerate. This presents a substantial challenge in managing kidney diseases, as the organ’s repair remains elusive in such cases. As Dr. Jie Zheng, a distinguished professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics and co-author of the study, states, “Your kidney will just fail sooner or later.”
Discovering this self-renewal mechanism marks a significant breakthrough. The potential implications of further research are promising, potentially leading to advancements in nanomedicine and the early detection of kidney diseases, according to Dr. Zheng.
The researchers stumbled upon this unexpected finding while investigating the filtration and clearance of gold nanoparticles by the kidneys. Previous research had shown that gold nanoparticles tend to pass through the glomerulus, a kidney structure, and subsequently enter the proximal tubules. Within these tubules, proximal tubular epithelial cells were found to internalize these nanoparticles, with unclear details regarding their eventual escape.
In December 2021, the research team, consisting of Dr. Zheng, lead study author Yingyu Huang, and co-corresponding author Dr. Mengxiao Yu, switched to an electron microscope for better resolution. There, they observed gold nanoparticles enclosed in lysosomes within large vesicles in the lumen, the space outside the epithelial cells. Moreover, they noted the formation of vesicles containing not only nanoparticles but also various organelles typically confined within cells. These vesicles, carrying the extruded contents, were released into the extracellular space. This unusual phenomenon signified a new method for cells to eliminate cellular contents.
This extrusion-mediated self-renewal mechanism stands apart from known regenerative processes like cell division or exocytosis. Unlike exocytosis, where foreign substances are encapsulated within a vesicle that fuses with the cell membrane to release the contents externally, this newly discovered process involves the elimination of old cellular contents from normal cells without membrane fusion. It allows the cells to refresh themselves with fresh materials, whether foreign nanoparticles are present or not.
The implications of these findings extend beyond kidney research. Epithelial cells, similar to those in the proximal tubules, are found in other tissues like artery walls, the gut, and the digestive tract, opening up new avenues for exploration. In the field of nanomedicine, understanding how nanoparticles are eliminated from the proximal tubules can help minimize their accumulation in the body. Additionally, gaining insights into regulating or monitoring this self-renewal process could lead to innovative approaches to maintain kidney health in patients with conditions such as high blood pressure or diabetes. Developing noninvasive methods to detect the signature of this process might serve as an indicator of early kidney disease.
The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Science Foundation, and the Cancer Prevention and Research Institute of Texas.