Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem Cells and ABC Transporters Essential in Kidney Regeneration

28.01.2009
In a study funded by the Dutch Kidney Foundation (DKF) a research group at Radboud University Nijmegen Medical Centre in the Netherlands, found that stem cells and ABC transporter proteins are indispensable for tubular regeneration after acute kidney injury (Journal of Pharmacology and Experimental Therapeutics, 2009 Jan; 328(1):3-9. Epub 2008 Sep 12).

Said project leader Dr. Rosalinde Masereeuw: 'To our surprise, our knockout mice for the ABC transporters P-gp and BCRP, P-gycoprotein and breast cancer resistance protein, were protected against acute kidney damage.

This was the opposite of what we expected since the transporters usually have a protective function in excreting potentially toxic compounds, while these mice lack expression. Moreover, when we cross transplanted bone marrow between normal mice and the knockouts it turned out that bone marrow from the knockouts was the source of protection.'

Regeneration
Acute kidney injury is an important cause for the need of acute hemodialysis and a source of kidney failure. On the other hand, the kidney has a remarkable capacity for recovery. Stem cells seemed to have a limited share in the repair process, but now this study suggests otherwise.

'It was known that stem cells from the bone marrow express P-gp and BCRP abundantly but will downregulate them at differentiation. Repair of tubular damage in the kidney depends primarily on local cells but stem cells are involved as well. Further, we observed an upregulation in the expression of the transporters during ischemic injury. .So we thought they might be important in renal regeneration.'

Transporter Proteins
ABC transporters (ATP binding cassette transporters) form a superfamily of highly conserved transporter proteins whose functions are not yet well understood. However, BCRP and especially P-gp have been studied in more detail in man. These cell membrane pumps are responsible for the transport of many substances, for instance drug molecules in the intestine. P-gp plays an important role in drug resistance of tumour cells.

Masereeuw: 'Our new hypothesis claims a bigger role for bone marrow derived stem cells in kidney regeneration. A possible mechanism is the infiltration of macrophages. These large immune cells have subgroups one of which increases damage but another supports tissue regeneration.'

Also, the study showed that mice without P-gp expression lose renal tubular function in a way comparable to Fanconi syndrome in man. BCRP knockouts, on the other hand, have a normal kidney function.

Blocking P-gp and BCRP
There is a great need for novel therapies that limit kidney damage after acute injury by toxic substances or shortage of oxygen, as in transplant kidneys which have no blood supply during transport. The results from this DKF study are pointing at inhibition of the transporters in kidney or bone marrow to strengthen the regenerative power of stem cells.

'Next, we will try to discover the mechanism by which stem cells and ABC transporters contribute to kidney repair', concludes Dr. Masereeuw, 'and we will test the effect of transporter blockers in our mouse models. We are convinced there are good opportunities here for new drug targets.'

Arjen Rienks | alfa
Further information:
http://www.nierstichting.nl

More articles from Studies and Analyses:

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

nachricht Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>