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School of Medicine
A surprise discovery may expand what is known about the kidney’s elaborate physiology
October 2010- Like a jazz musician, nature riffs on its successful themes. And so it appears that the ability to “smell” may not be unique to the nose. Jennifer Pluznick, an assistant professor of physiology at Johns Hopkins, has found that the odor-sensing proteins found in the noses of mice also occur in their kidneys. The same olfactory receptors may also exist in the human nose, she says.
But could it be that the kidney is actually endowed with a sense of smell?
Not exactly, says Pluznick. “It’s going too far to say the kidney is smelling, although it’s kind of fun to think of it that way.” She prefers the term sniffing. “The kidney is sniffing the urine as it goes by.”
While the kidney and nose may appear to be as distant in function as they are in anatomy, in fact, says Pluznick, both are tasked with the same initial job: identifying the chemicals in their environment. The nose has hundreds of different odorant receptors for this job. Each odor stimulates a different receptor or ensemble of receptors, launching a cascade of signaling events that channel the message (lemon, skunk, burning rubber) to the brain.
For its part, the kidney filters all of the body’s blood about 30 times each day, excreting foreign substances that may harm the body, and reabsorbing or excreting just enough water, sodium, potassium and other electrolytes to maintain the body’s finely tuned homeostasis. “It’s an exquisite point of control,” says Pluznick. “The kidney jealously guards the concentrations of what ends up in the blood versus the urine.”
How does the kidney “know” what to keep and what to toss? Pluznick hypothesizes that for some substances, the kidney may use the same molecular trope as the nose: the olfactory signaling system.
The finding “is novel and unsuspected,” says Terry Watnick, a Hopkins nephrologist who studies the genetics of polycystic kidney disease. “The kidney has to sense a lot of different cues. While there are some well-known pathways that explain this regulatory process, obviously there may be others.”
Pluznick says she “stumbled upon” the olfactory signaling system in the kidney during her postdoc at Yale, where she was studying a gene called polycystin 1, which is mutated in some cases of polycystic kidney disease. She hypothesized that the gene regulates other genes in the kidney, and that those interactions contribute to the disease. So Pluznick used a microarray, or “gene chip,” to identify what those other genes might be. The gene chip contained thousands of different gene-containing DNA bits, each in its own micro well. Pluznick used cells containing polycystin 1 protein to screen the microarray. If polycystin 1 regulated any gene on the chip, the well containing that gene would “light up.” Indeed, some wells did light up, and to Pluznick’s surprise, some of those wells contained olfactory genes.
At first Pluznick was perplexed and assumed that she had made a mistake. Why would olfactory genes be expressed in the kidney? But further tests confirmed her result. Now Pluznick was intrigued. With further thought, she saw the logic in the parallel systems: Just as the nose requires a chemical sensor, so might the kidney.
There was also, Pluznick learned, a precedent in the scientific literature for olfaction—or, some version of it—outside of the nose. Scientists had reported that human sperm contain odor-receptor proteins, which the sperm may use to “smell” their way to the egg.
Since arriving at Hopkins in July, Pluznick has continued to explore the role of the olfactory signaling system. One question is whether the proteins are indeed functioning as chemical sensors and, if so, what molecules they are sensing. She is also looking to see where in the kidney’s complex of tubules, nerves and blood vessels the olfactory receptors are located. “If we can do that, then we can make inferences about what roles the receptors are performing,” she says.
Eventually, expanding what is known about how the kidney performs its vital role could reap clinical applications. “We don’t completely understand how the kidney helps maintain the body’s homeostasis,” says Pluznick. “Learning more could help us understand what’s going on with patients who have imbalances.”