The findings suggest manipulating activity of PKD1, the gene causing the most common form of polycystic kidney disease, may prove beneficial in reducing cysts in both liver and kidney.
"We found that these conditions are not the result of an all or nothing phenomenon," said Stefan Somlo, the C.N.H. Long Professor of Medicine and Genetics and Chief, Section of Nephrology and senior author of the study. "The less PKD1 is expressed, the more cysts develop. Conversely, expressing more PKD1 can slow the process."
The most common form of this condition is called autosomal dominant polycystic kidney disease (ADPKD), a condition passed on to children from one parent affected with the disease that is found in 600,000 people in the United States alone. Two genes, PKD1 and PKD2, are responsible for the onset of this condition.
PKD patients also develop cysts of the liver and Somlo and colleagues had previously identified families with identical cysts found only in the liver. They found two different genes were responsible for this related condition.
The researchers wanted to know how liver-only polycystic disease was related to ADPKD. In a series of experiments using both genetically engineered mouse models and biochemical studies, they found that the activity of only one of the four genes, PKD1, controlled cyst formation in the other forms of the disease. Experiments in mice showed that modulating dosage of PKD1 could slow disease progression.
"The data suggest the exciting possibility that targeting the activity of PKD1 may be beneficial for treatment of isolated polycystic liver disease, childhood recessive polycystic kidney disease and even a subset of adult ADPKD," said Somlo.
Yale is a leader in the investigation of PKD. For instance basic scientific research conducted at Yale has been crucial in helping to identify cilia, the tiny thread-like structure that extends from a cell's surface, as a critical component in cyst forming pathways. Yale has been the home of one of the four NIH-funded national centers of excellence in PKD research since 1999. In addition, the laboratory of Craig Crews, Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology and Professor of Chemistry and of Pharmacology, has identified a compound that has shown promise in reducing number of cysts in some mouse models of PKD.
Sorin V Fedeles, Xin Tian, Anna-Rachel Gallagher, Michihiro Mitobe, Saori Nishio, Seung Hun Lee, Yiqiang Cai, Lin Geng and Craig Crews of Yale are co-authors of the paper.
The work was funded by the National Institutes of Health
Bill Hathaway | EurekAlert!
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences