Faulty gene regulation triggers the kidney disease FSGS

March 20, 2013, Medical University of Vienna
Faulty gene regulation triggers the kidney disease FSGS

The Clinical Institute of Pathology at the MedUni Vienna has discovered a previously unknown mechanism in the regulation of gene expression that leads to the development of a chronic renal condition known as focal segmental glomerulosclerosis (FSGS). Primary FSGS is currently untreatable and can lead to secondary conditions ranging from nephrotic syndrome with severe oedema to the destruction of renal function.

"The build-up of substances that are normally excreted in the urine in the patient's blood poisons the entire body and can only be prevented through long-term dialysis or renal transplant," says Dontscho Kerjaschki, Head of the Clinical Institute of Pathology at the MedUni Vienna.

FSGS is a in which parts of the urine-forming, microscopically small organs (known as renal glomeruli) gradually become more and more scarred. This slowly causes the kidneys' filtering function to deteriorate, even though the patient may not notice it. The renal glomeruli – of which we have around one million in each kidney – contain highly specialist that monitor filtration output and prevent important proteins (such as ) from being lost from the blood into the urine.

These cells are the target of FSGS. One international "hot topic" in the research of is the discovery of the molecular causes of this condition, as a basis for developing a targeted form of therapy that is not yet currently available. "In around 20 per cent of cases of FSGS, there is a , and in around 30 per cent there is an obvious circulatory factor that can trigger the recurrence of the disease in a transplanted organ. But for the remaining 50 per cent, we have so far been unable to determine any cause," says Kerjaschki.

In collaboration with the group led by Javier Martinez at the IMBA (Institute of ), the scientists at the MedUni Vienna have discovered the direct cause of the damage in the largest group of cases. They have demonstrated that a certain micro-RNA (mir-193a) is massively over-produced in the critical glomerular cells and switches off the entire spectrum of essential, coordinated gene regulation in these cells. This damages the cells of the filtration system so badly that it can lead to the collapse of their filtration capacity and the blood-urine barrier is destroyed. Building on these results, further studies are planned which aim to determine "why mir-193a is overexpressed", says Kerjaschki, "what causes this and how we can find a targeted way to switch off this disease-causing system."

Kerjaschki summarises the outcome of the study, which has now been published in the highly respected journal Nature Medicine, as follows: "Micro-RNA mir-193a switches off the vital regulation of the most important cells for . This publication in Nature Medicine, the most competitive journal in translational medicine with an impact factor of 22.4, is now the sixth from the MedUni Vienna's Clinical Institute since 2004. Each year, around 1,600 renal biopsies are performed every year at the MedUni Vienna's Clinical Institute of Pathology, one of the largest centres for renal biopsies in Europe, and around 50 of these yield a diagnosis of FSGS.

Explore further: Circulating blood factor linked with a leading cause of kidney failure

More information: Gebehuber, C. et al. Focal and segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1, Nature Medicine. doi:10.1038/nm.3142

Related Stories

Circulating blood factor linked with a leading cause of kidney failure

November 8, 2012
Patients with a disease that is a leading cause of kidney failure tend to have high levels of a particular factor circulating in their blood, according to a study appearing in an upcoming issue of the Journal of the American ...

Kidney transplanted twice in two weeks

April 25, 2012
For the first time, a kidney that had been donated to a patient in need was removed and implanted into a new patient, the third individual to have the organ, after it failed in the first transplant recipient. Ray Fearing, ...

Recommended for you

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Zika virus damages placenta, which may explain malformed babies

January 18, 2018
Though the Zika virus is widely known for a recent outbreak that caused children to be born with microencephaly, or having a small head, and other malformations, scientists have struggled to explain how the virus affects ...

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018
Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations ...

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

LarryDahl
not rated yet Mar 29, 2013
I wonder if a parental contact with agent Orange in Vietnam could cause this problem

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.