Surprising mechanism discovered in polycystic kidney disease

A study by Yale researchers has uncovered a new and unexpected molecular mechanism in the development of polycystic kidney disease, or PKD. The study appears in Nature Genetics.

PKD is a life-threatening genetic disorder that causes multiple cysts to form on the kidneys—enlarging them, cutting off proper urine flow, and causing in half of affected people by age 60. It affects more than 12 million people worldwide.

Cilia are the hair-like structures on the surface of many that can either move things along – dirt out of the lungs, or an egg from the ovary to the uterus – or sense the environment, such as vision in the retina or smell in the nose. Recent research has implicated defects in the sensory cilia—often caused by —in many human diseases, including cancer, cardiac disease, blindness, and kidney disease. In the kidney, disruption of sensory cilia cause kidney cysts.

The polycystin-1 and -2 (also known as PC1 and PC2) proteins are key players in the normal functioning of the kidneys. Earlier research has shown that when they are lost or mutated, cysts grow in the kidneys and cause almost all cases of PKD in humans.

Working in mice, the Yale team found that cysts grew when the cilia were intact but lacked polycystin—but, surprisingly, cysts stopped growing despite the absence of polycystins when the cilia were disrupted or eliminated.

The activity of this pathway, and the timing of the loss of polycystin proteins and the cilia, determined the severity of both early- and adult-onset PKD, the researchers found.

"None of the other pathways discovered so far have proven as universal as the cilia dependent pathway in explaining polycystic ," said corresponding author Dr. Stefan Somlo, professor of internal medicine (nephrology) and genetics at Yale School of Medicine. "We found to our surprise that elimination of cilia suppresses cyst growth in all of the of human PKD."

Somlo believes that his team's research could lead to discovery of new targets for therapies to inhibit this cilia-dependent pathway of PKD, and slow cyst growth.

More information: Nature Genetics DOI: 10.1038/ng.2715

Related Stories

Aurora A may contribute to kidney disease

Jun 13, 2011

The Aurora A kinase may contribute to polycystic kidney disease (PKD) by inactivating a key calcium channel in kidney cells, according to a study in the June 13 issue of The Journal of Cell Biology.

Researchers identify new role for cilia protein in mitosis

Apr 04, 2011

Researchers at the University of Massachusetts Medical School have described a previously unknown role for the cilia protein IFT88 in mitosis, the process by which a dividing cell separates its chromosomes containing the ...

Experiments point to new treatments for PKD

Apr 02, 2008

A family of small molecules called CFTR inhibitors show promising effects in slowing the progression of polycystic kidney disease (PKD), the most common genetic disease of the kidneys, according to preliminary research reported ...

Recommended for you

Down's chromosome cause genome-wide disruption

3 hours ago

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

Research uncovers DNA looping damage tied to HPV cancer

9 hours ago

It's long been known that certain strains of human papillomavirus (HPV) cause cancer. Now, researchers at The Ohio State University have determined a new way that HPV might spark cancer development – by ...

New therapy against rare gene defects

Apr 15, 2014

On 15th April is the 1st International Pompe Disease Day, a campaign to raise awareness of this rare but severe gene defect. Pompe Disease is only one of more than 40 metabolic disorders that mainly affect children under ...

User comments