In genetically modified mice, scientists at Washington University School of Medicine in St. Louis captured images of a defective version of a kidney structure leaking a substance from the blood into the urine. The images suggest that the structure, known as the glomerular basement membrane (GBM), normally plays a key role in keeping blood proteins out of the urine.
The finding, reported in the August issue of the Journal of Clinical Investigation, will help doctors understand nephrotic syndrome, a condition with symptoms that include blood proteins in the urine. The syndrome can be triggered by a variety of genetic and environmental factors and leads to kidney failure over a varying time period.
"All the treatments we now use for nephrotic syndrome are either non-specific, meaning that we can't say for sure that they directly address the problem, or they are toxic," notes lead author George Jarad, M.D., a postdoctoral research scholar. "The first step to developing a specific treatment is to understand exactly what's happening. We have to know the details of the process before we can devise a remedy."
The new results are a reversal for nephrologists, who until a decade ago had long suspected the GBM was the primary barrier that retained blood plasma proteins. In the late 1990s, though, a Finnish research team bumped another structure, the slit diaphragm, into the position of prime suspect. They showed that a mutation in one of the proteins that make up the slit diaphragm caused a form of kidney disease that led to protein in the urine.
Both the slit diaphragm and the GBM are found in the glomeruli, small structures within the kidney that filter wastes from the blood and release them into the urine. Normally a small amount of blood protein leaks into the urine via this process and can be resorbed by the kidneys; however, when protein leakage levels go too high, scientists suspect this triggers a series of chain reactions that lead to kidney failure.
For their study, Jarad and colleagues in the labs of Jeffrey Miner, Ph.D., associate professor of medicine and cell biology and physiology, worked with mice lacking the gene for laminin beta 2, a protein that is part of the GBM. Two years ago, scientists linked a human mutation in the gene for laminin beta 2 to an inherited disorder that causes kidney disease and abnormalities in the eye and the neuromuscular system.
Scientists gave the mice ferritin, a protein often used as an imaging agent because it is easily detected by electron microscopes. They then used an electron microscope to take pictures of ferritin in the kidney and found it slipped more readily through the GBM in the genetically modified mice than it did in normal mice.
How comparable is ferritin to the blood proteins nephrologists are concerned about?
"Ferritin is actually much bigger than most blood proteins," Miner notes, "but other scientists have previously shown that, like blood proteins, ferritin is normally retained by the kidney."
Miner suspects--but cannot yet prove--that the problems in the slit diaphragm detected by the Finnish team may slow the ability of water to pass through the diaphragm and into the urine without affecting the passage of blood proteins. This could increase the concentration of protein passed into the urine without increasing the actual quantity of protein passed.
"It may be that the GBM is what determines the absolute amount of protein that's able to cross over into the urine, and the slit diaphragm and related structures determine its concentration," he explains. "It's a very complicated combination of fluid dynamics and physiology that we're still sorting out."
Miner and others are now working to determine how leakage of blood proteins through the GBM may lead to damage in structures beyond the membrane, potentially initiating a series of chain reactions that lead to kidney failure. They are also hoping to learn more about the kidneys' capabilities for resorption of proteins that have leaked into the urine.
Michael C. Purdy | EurekAlert!
'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS
New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
19.02.2018 | Information Technology
19.02.2018 | Ecology, The Environment and Conservation
19.02.2018 | Life Sciences