December 4, 2018
New research has found that how cells in the kidney communicate with and respond to one another could be the key to preventing kidney failure in chronic kidney diseases.
The collaborative study, led by the Westmead Institute for Medical Research,found the key factor causing kidney fibrosis – known as TGF-β – can be used rather precisely to prevent kidney failure.
Fibrosis is scarring of the kidney, a common result of all chronic kidney diseases, which can lead to end stage kidney disease (kidney failure). Patients with end stage kidney disease require a kidney transplant or dialysis to survive.
It is estimated 1.7 million adult Australians show signs of chronic kidney disease. 21,000 Australians receive kidney replacement therapy and many more die of kidney failure as a result of kidney fibrosis.
The research showed that blocking the interaction between two key proteins (β-catenin and T cell factor) allows TGF- β to be used to prevent kidney fibrosis.
Lead researcher Dr Guoping Zheng said their research showed, for the very first time, that changing how cells in the kidney respond can reduce kidney fibrosis.
“Our research shows that stopping these two proteins from interacting kick starts another process that reduces inflammation and fibrosis in the kidney at same time, killing two birds with one stone,” Dr Zheng said.
TGF-β plays an important role in protecting the kidney from inflammation, but paradoxically can also lead to fibrosis.
Dr Zheng said that previous studies have attempt to completely block the function of TGF-β, which can actually increase fibrosis.
“Our world first study has resolved decades of controversy around the role of TGF-β in kidney fibrosis,” Dr Zheng said.
“TGF-β has a dual role. While it can contribute to fibrosis, it also plays an important role in protecting the kidney by reducing inflammation.
“Blocking this protein entirely also blocks its protective functions and has been proven ineffective in recent clinical trials.
“Rather than blocking TGF-β, we found that by pointing it in the right direction we can make it work for us to actually reduce fibrosis,” Dr Zheng said.
The team found that blocking the interaction between β-catenin and T cell factor encouraged β-catenin to bind with another protein, called Foxo, and this process plays a vital role in fighting inflammation in the kidney.
“We hope this positive interaction between TGF-β and Foxo could be used in to develop new therapies to prevent fibrosis and treat patients with kidney disease,” Dr Zheng concluded.
We hope these findings can be used in to develop new therapies to prevent fibrosis and treat patients with kidney disease.
Dr Zheng and his team are now working to translate their findings to clinical application in treating chronic kidney diseases and inflammatory fibrotic diseases of other organs.
The paper was published in the Journal of the American Society of Nephrology: https://jasn.asnjournals.org/content/29/2/557
The research was published in collaboration with colleagues from: the Westmead Institute for Medical Research; The University of Sydney; Shanxi Medical University: and the Kids Research Institute, Westmead.