A study funded by the United States National Institutes of Health (NIH), in which both mice and patients participated, has discovered that a gene, called PIEZO2, may be responsible for the powerful urge to urinate that we normally feel several times a day.
The results, published in the scientific journal Nature, suggest that the gene helps at least two different types of cells in the sense of the body when our bladders are full and need to be emptied. These results also expand the growing list of newly discovered senses under the gene’s control.
Urine is produced when the kidneys remove waste and excess water from the blood and send it to the bladder. Over time, it fills up and expands like a balloon, putting stress on the bladder muscles. So at a certain point, the body feels that it is reaching a limit, what triggers the need to urinate.
He gen PIEZO2 It contains instructions for making proteins that are activated when cells are stretched or squeezed. In this study, the researchers found that patients born with a genetic deficiency in PIEZO2 they have trouble feeling bladder fullness, while experiments in mice suggested that the gene plays two critical roles in this process. It can help certain cells in the bladder measure expansion, while also causing neurons to transmit stress signals to the rest of the nervous system.
In 2010, this team of scientists discovered the PIEZO2 gene along with a similar gene called PIEZO1 in a line of mouse brain tumors. Before that, scientists knew of only a few rare examples of flies, worms and mice in which a gene helped tissues, such as hairy skin cells, to perceive changes in shape and pressure. Since the discovery, this team and others have shown primarily in mice that the PIEZO2 gene can play many roles throughout the body, including control of the sense of touch, vibration, pain and proprioception, the unconscious awareness of one’s own body in space.
In 2015, there was a breakthrough. Researchers discovered people who were born with disabling mutations in your PIEZO2 genes. Initial evaluations of these PIEZO2-deficient individuals replicated some of the results from mice. They had no sense of proprioception Y they couldn’t feel some forms of touch and pain.They also had something else in common.
“We were very surprised by what we heard during interviews with patients and their families. Almost everyone mentioned that patients had trouble urinating. When they were kids, they had trouble going to the bathroom. They often had urinary tract infections. And most of them follow a daily urination schedule. After seeing a consistent pattern, we decided to take a closer look, “explains one of the authors of the research, Dimah Saade.
The researchers examined medical records, conducted ultrasound scans, questionnaires, and detailed interviews with 12 patients, ages 5 to 43, and their families. Almost all stated that they could go a whole day without feeling the need to urinate and most urinated less than normal five or six times a day. In fact, three patients reported that they only went once or twice a day. Five patients said that when they finally feel a need, it appears as an abrupt impulse. Seven noted that the act of urinating was difficult. They had to wait for it to happen or they had to put pressure on the lower abdomen for it to start.
In mice, the researchers initially found that the PIEZO2 gene was highly active in a few neurons of the dorsal root ganglion (DRG) that send nerve signals from the bladder from the mouse to the brain. With the help of an advanced real-time imaging system, they saw cells light up with activity when a mouse’s bladder filled with fluid. They also found that the PIEZO2 gene was turned on in some ‘umbrella’ cells that lie between the cells lining the inside of the bladder.
Then they found that delete gene of neurons and ‘umbrella’ cells not only reduced the cells’ response to bladder filling, but also caused the mice to had trouble urinating. The ‘mutant’ mice showed some signs of incontinence and they urinated randomly in their cages rather than in a corner as seen in control mice. Meanwhile, the bladders of the mutant mice required more fluid and higher pressure than normal to trigger urination, reminiscent of patient reports.
They also discovered that gene deletion of the two types of cells had longer lasting effects. For example, the bladder muscles of the mutants were thicker than those of the controls, suggesting that the loss of sensation reshaped the bladder.
Ultimately, the researchers found that delete the PIEZO2 gene of ‘umbrella’ cells or DRG neurons produced similar results to those of erasing them from both types of cells simultaneously. Removing the gene from either cell lengthened the time it took for the mice to feel the need to squeeze their bladders and increased the pressure applied during each squeeze.
In the future, researchers will continue examining the role of PIEZO2 in urination and other interoceptive senses, while also exploring the clinical implications of their discovery for the millions of people who suffer from urinary control problems.