Scientists may be one step closer to unlocking the secrets behind the kidney healing process.
Researchers from the Cedars-Sinai Medical Center in Los Angeles, California, have detailed a new study that explains why some kidneys heal after an injury while others remain scarred. Scientists hope that this research can be used to develop, treat, and even reverse kidney scarring.
Sanjeev Kumar, MD, Ph.D., senior author of the study and a nephrologist-scientist at Cedars-Sinai, identified several ways kidneys could be damaged, such as overuse of medication, hypertension, diabetes, and more. Some of these conditions are linked to other conditions, such as obesity.
In the new study, published in the peer-reviewed journal Science on February 23, scientists conducted studies on the damaged kidneys of mice in a laboratory setting, labeling individual cells at the injury and documenting their development reproduction, noting a particular protein called SOX9. This protein is present when organs are developing and is no longer active when a subject reaches adulthood.
Kumar and another team found that kidneys reactivate this protein when injured. Kumar explained that when the protein is deactivated again in a “timely fashion,” no scarring is left behind. The researchers also discovered that the cells unable to regenerate began using proteins called Wnts. The accumulation of these proteins triggered kidney scarring.
“At Day 10, some cells’ descendants were fully healed while others were not,” said Kumar, according to a press release. “The cell lineage that healed had switched off SOX9 expression, while the unhealed lineage, in a continuing attempt to fully regenerate, maintained SOX9 activity. It’s like a sensor that switches on when cells want to regenerate, and off when they are restored, and we are the first to identify this.”
Kumar noted similar reports in human trials undertaken by Swiss and Belgian scientists.
“We could see that by Day 7, human patients with transplanted kidneys that were slow to begin working also activated SOX9,” said Kumar in the release. “And in our collaborators’ database, we were able to distinguish that patients who had sustained SOX9 activation had lower kidney function and more scarring than those who did not. Human kidneys with cells that maintained SOX9 were also enriched with Wnts and showed increased fibrosis.”
Researchers hope these findings can be used to develop noninvasive testing and medication to treat kidney scarring.
“These findings help us understand for the first time how the kidney’s response to injury sometimes leads to fibrosis,” said Clive Svendsen, Ph.D., a co-author of the study, according to the release. “Future work along these lines could also advance our understanding of fibrosis in the heart, lungs and liver.”
