Hibernating bears provide clues for kidney regeneration
By Mark Wanner
Black bears hibernate for up to seven months out of every year. And while it seems like a great way to get through cold winters, the reality is that months of much lower metabolism is tough on the body. How do bears endure long periods of minimal kidney function and damage, yet quickly recover from it each spring?
The answers could help scientists develop therapies for human kidney conditions, a growing health problem that currently affects 14% of U.S. residents and more than 20% of the global elderly population. Unlike bears, once kidney damage occurs in humans, it is permanent with no options other than kidney transplants or long-term dialysis.
In a paper published online in DNA Research, “Genome assembly and gene expression in the American black bear provides new insights into the renal response to hibernation,” a team led by JAX Assistant Professor Ron Korstanje presents intriguing data regarding bear kidneys and their function. The researchers sequenced RNA from bear kidneys to determine relative gene expression in the kidneys between spring, soon after the bears emerge from hibernation, and fall, before they return to their dens for the winter. Overall, the RNA analysis indicated changes in expression for 169 genes, with 101 lower and 68 higher in spring compared to fall.
There was a particularly notable group of upregulated genes in the spring, all involved with cytokine suppression. Cytokines normally serve as signals to activate immune system function, and dysfunction can lead to inflammation. A hallmark of bear hibernation is that despite pro-inflammatory risk factors for the kidneys, there are no signs of systemic inflammation.
Suppressing this aspect of immune activation may be a key component of the bear kidney’s resilience. Importantly, many human patients with chronic kidney disease have systemic inflammation as well, and it is associated with poor outcomes.
For help obtaining bear kidney tissue, Korstanje’s team turned to local Native American tribes who provide a very limited number of permits to hunters during the spring and fall seasons. Collaborating with the tribes and hunters for samples meant that no additional bears were hunted for research.
Korstanje also completed a high quality, annotated genome sequence, the first for the black bear, providing a foundation for subsequent inquiries.
While the further exploration of the anti-inflammatory pathways activated in hibernating bears is needed, the preliminary findings indicate that anti-inflammation treatment regimens offer a potential strategy for human therapy.