Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rogue receptor opens door for rare kidney disease

26.09.2011
Effects of a particularly devastating human kidney disease may be blunted by making a certain cellular protein receptor much less receptive, according to new research by scientists from North Carolina State University and a number of French universities and hospitals.

The findings take a major step toward suggesting a beneficial treatment for rapidly progressive glomerulonephritis (RPGN), a rare but debilitating kidney disease that causes renal failure and death in humans.

In a paper published online in Nature Medicine, the researchers show that blocking the ability of the epidermal growth factor (EGF) receptor – an important component in wound healing – to bind with certain molecules in the kidneys of mice can eliminate the harmful effects of a mimic version of RPGN.

EGF receptors act like important keyholes on a cell's surface, says Dr. David Threadgill, professor and head of NC State's Department of Genetics and a co-author of the paper. Certain keys, or in this case molecules, can fit with the receptor and "open the door" to a cascade of cellular processes leading to inflammation, which can be good when your body needs to heal a wound or a cut. It's bad, however, when the inflammation runs amok, as when RPGN takes hold.

How important are EGF receptors in RPGN? When EGF receptors were taken out of the equation – through special mice from Threadgill's lab that were genetically engineered without EGF receptors – the disease was unable to take hold and degenerate kidney tissues.

The study also showed that certain drugs that inhibit EGF receptors – think of them as pieces of gum in the keyholes – not only prevented mouse kidneys from degrading but also reversed the harmful effects four days after mice were exposed to the RPGN mimic.

"EGF receptors are essential components for life, but are implicated in not only RPGN but also a number of cancers like colon cancer and breast cancer," Threadgill says. "They must be tightly regulated. If we can inhibit these receptors for short periods of time, we may be able to stop out-of-control cell proliferation and inflammation and thus prevent or treat certain cancers or diseases."

The Department of Genetics is part of NC State's College of Agriculture and Life Sciences.

"The Epidermal Growth Factor Receptor Promotes Glomerular Injury and Renal Failure in Rapidly Progressive Crescentic Glomerulonephritis; the Identification of Possible Therapy"

Authors: Martin Flamant, Universite Paris-Diderot; Guillaume Bollee, Universite Paris-Descartes; David Threadgill, North Carolina State University, et al

Published: Online Sept. 25, 2011, in Nature Medicine

Abstract: Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome and a morphological expression of severe glomerular injury. Glomerular injury manifests as a proliferative histological pattern, accumulation of T cells and macrophages, proliferation of intrinsic glomerular cells, accumulation of cells in Bowman's space ("crescents"), and rapid deterioration of renal function. Here we show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the EGFR/ErbB1 receptor in mice with anti-GBM disease. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is markedly improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates crescentic glomerulonephritis and the clinical features that accompany RPGN. Finally, pharmacological blockade of EGFR also prevents nephrotic syndrome, infiltration of T cells and macrophages, necrotizing crescentic glomerulonephritis, acute renal failure and death in mice. This approach is effective even when started 4 days after the induction of experimental RPGN, suggesting that targeting the HB-EGF/EGFR pathway could also be clinically beneficial for treatment of human RPGN.

Mick Kulikowski | EurekAlert!
Further information:
http://www.ncsu.edu

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>