Researchers from the Texas University in Dallas have found a previously unidentified” housekeeping” process in kidney cells that ejects unwanted material, causing the cells to regenerate and continue to function and be healthy.
The self-renewal process, which differs fundamentally from how other bodily tissues are thought to regenerate, aids in explaining how, barring injury or disease, the kidneys can live a lifetime in good health. In a study that was released on April 17 in Nature Nanotechnology, the researchers described the mechanism.
In contrast to the liver and skin, where cells divide to produce new daughter cells and regenerate the organ, kidney cells in the proximal tubules are mitotically quiescent and do not divide. According to Dr. Jie Zheng, a professor of chemistry and biochemistry at the School of Natural Sciences and Mathematics and the study’s co-author, kidney cells do have limited repair capabilities in cases of mild injury or disease, and stem cells in the kidney can form new kidney cell, but only to an extent.
Most of the time, kidney cells that have been severely damaged will die and be unable to regenerate. Sooner or later, your kidney will just stop working. That presents a significant obstacle in kidney disease health management. Right now, the only thing we can do is halt the progression toward kidney failure. If the organ is severely damaged or by a chronic disease, we cannot easily repair it.
Finding this self-renewal mechanism is therefore likely one of the most important discoveries we have made to date. UTD is a great place to conduct such cutting-edge research thanks to its excellent core facilities and committed staff.
Distinguished Chair in Natural Sciences and Mathematics, Dr. Jie Zheng
According to him, additional research could result in advancements in nanomedicine and early kidney disease detection.
Unexpected discovery
The researchers claimed that they were surprised by their discovery.
Zheng has been researching the biomedical use of gold nanoparticles as imaging agents for 15 years in order to better understand glomerular filtration, identify liver disease early on, and deliver cancer drugs specifically to patients. Understanding how gold nanoparticles are filtered by the kidneys and eliminated from the body through urine has been a main focus of that research.
According to research, gold nanoparticles typically pass unharmed through the kidney’s glomerulus before entering the proximal tubules, which make up more than 50 % of the organ. It has been demonstrated that tiny tubular epithelial cells internalize the nanoparticles, which then escape and are excreted in urine. But it’s unclear exactly how they get out of the cells.
Zheng and his chemistry team were using an optical microscope to examine gold nanoparticles in proximal tubular tissue samples in December 2021. However, they switched to one of the University’s electron microscopes ( EM ) for better resolution. They were led by research scientist and lead study author Yingyu Huang PhD’20 and co-corresponding author Dr. Mengxiao Yu.
According to Yu,” Using the EM, we observed gold nanoparticles encapsulated in lysosomes inside of sizable vesicles in the lumen, which is the area outside the epithelial cells.”
Vesicles are tiny fluid-filled sacks that can be found both inside and outside of cells that carry different substances.
However, Yu added,” We also noticed the formation of these vesicles, which contained both nanoparticles and organelles outside of cells, and it was something we had never seen before.
The scientists discovered proximal tubular cells with bulges in their luminal membranes that had grown outwardly facing and contained not only gold nanoparticles but also lysosomes, mitochondria, endoplasmic reticulum, and other organelles that are typically found inside a cell. After being pinched off into a vesicle, the extruded contents floated into extracellular space.
We were aware that this was an unusual occurrence at the time, Yu said. This is a brand-new technique for removing cellular contents from cells.
a fresh renewal procedure
The extrusion-mediated self-renewal mechanism is fundamentally distinct from other well-known regenerative processes, like cell division, and housekeeping tasks like exocytosis. Foreign substances like nanoparticles are encapsulated in a vesicle inside the cell during exocytosis. The cell’s membrane then opens to release the contents to the outside as a result of the vesicle membrane fusing with the interior membrane.
” What we found is completely different from what was previously known about how cells get rid of particles.” The extrusion process does not involve membrane fusion, which removes old content from healthy cells and enables them to update themselves with new contents, according to Huang. Whether or not there are foreign nanoparticles, it happens. These cells use an innate, proactive process to live longer and carry out their proper functions.
Their findings, according to Zheng, open up new research directions. For instance, epithelial cells can be found in other tissues like the proximal tubules, the gut, and the digestive tract, as well as the walls of arteries.
” In the field of nanomedicine, we want to reduce the body’s ability to accumulate nanoparticles as much as possible. It’s crucial to comprehend how nanoparticles are removed from the proximal tubules because we don’t want them to become stuck in the kidneys,” Zheng said.” Additionally, we might be able to keep kidneys healthy in patients with diabetes or high blood pressure if we could figure out how to control or monitor this self-renewal process.
” Perhaps this process could be a sign of early kidney disease if we could find ways to detect its signature noninvasively.”
The National Science Foundation, the Cancer Prevention and Research Institute of Texas, and the National Institutes of Diabetes and Digestive and Kidney Diseases( R01DK124881, R01MK115986 ) provided funding for the study.