Scientists at the University of Texas at Dallas have discovered a previously unknown “housekeeping” mechanism in kidney cells (Deep research shows how the kidney cells make themselves) that removes unwanted substances, allowing cells to regenerate and maintain work and health.
The process of regeneration, which is very different from how other tissues are supposed to regenerate, helps explain how, in the absence of injury or disease, the kidney can maintain good for life. The researchers described the process in a study published April 17 in Nature Nanotechnology.
Unlike the liver and skin, where cells divide to create new daughter cells and regenerate the organ, the cells in the proximal tubules of the kidney are silent – they do not divide to create new cells. In the case of mild injury or disease, kidney cells have limited repair capacity and kidney cells can generate new kidney cells, but only for a certain period of time, Dr. Jie Zheng, professor of chemistry and biochemistry at the School of Natural Sciences and Mathematics said. and the corresponding author.
“In most cases, if the kidney cells are seriously injured, they will die and will not be able to reproduce,” said Zheng, who holds a master’s degree in natural sciences and mathematics. “Your throat will die soon. It is a big challenge in the healthcare for kidney disease. All we can do now is to slowly move forward with kidney failure. We can’t repair that part of the body quickly if it’s severely injured or chronically ill.
“That’s why the discovery of this self-renewal process could be one of the most important discoveries we’ve made so far. With a good company and dedicated staff, UTD is a great place to do research is terrible.
Further research could lead to advances in nanomedicine and early detection of kidney disease, he said. An unexpected discovery
The researchers said they were surprised by their findings.
For 15 years, Zheng has studied the biomedical use of gold nanoparticles as photoreceptors, for the basic understanding of glomerular filtration, for the early diagnosis of liver disease, and for the delivery of anti-cancer drugs. Part of this work focused on understanding how the blood clears gold nanoparticles and removes them from the body through urine.
Studies have shown that gold-producing substances usually pass through the kidney called glomerulus without harm and enter the proximal tubules, which make up more than 50% of the kidney. Proximal tubular epithelial cells have been shown to absorb nanoparticles, which eventually escape into these cells to be excreted in the urine. But how they escape from the cells is not clear.
In December 2021, Zheng and his chemical team – researcher and leader of the study Yingyu Huang PhD’20 and corresponding author Dr. Mengxiao Yu, research professor – examines gold nanoparticles in samples of proximal tubular tissue using a light microscope. , and switched to one of the University’s electron microscopes (EM) for better resolution.
“Using EM, we saw the gold nanoparticles encapsulated in lysosomes in large vesicles in the lumen, which is the space outside the epithelial cell,” Yu said. Vesicles are fluid-filled sacs found inside and outside the body that carry various substances.
“But we also saw the formation of these vesicles containing both nanoparticles and organelles outside the cells, and that’s not something we’ve seen before,” Yu said.
The researchers found nearby tubular cells that formed protrusions facing the outside in their luminal membranes that contained not only gold nanoparticles, but also lysosomes, mitochondria, endoplasmic reticulum and other organelles that are normally closed. The removed particles are deposited into vesicles that float in the extracellular space.
“At the time, we knew this was unusual,” Yu said. “This is a new mechanism for cells to shed cellular contents.”
Renewal process
The self-renewal process is different from the known renewal process – like cell division – and the purification process like exocytosis. In exocytosis, foreign substances such as nanoparticles are inserted into vesicles inside the cell. Then, the vesicle membrane fuses with the cell membrane, which opens to release its contents to the outside.
“What we discovered is very different from previous understandings of how cells remove debris. There is no membrane fusion in the extrusion process, which removes the old content from the normal cells and allows the cells to have new content,” said Huang. “It happens whether foreign nanoparticles are present or not. It is an important and effective process.
Zheng said their findings open up new areas of study. For example, epithelial cells, such as those in the proximal tubules, are found in other tissues, such as the walls of arteries and in the intestines and digestive tract.
“In terms of nanomedicine, we want to reduce the concentration of nanoparticles in the body as much as possible. We don’t want them to stick to the kidneys, so understanding how to eliminate nanoparticles in the nearby tubules is very important,” Zheng said. “Furthermore, if we can learn to regulate or monitor our own self-renewal process, we can find ways to improve kidney function in patients with high blood pressure or diabetes.
“If we can develop a way to detect the signature of this process non-invasively, perhaps this could be an early indicator of kidney disease.”
Source: University of Texas at Dallas
