VCU School of Medicine researchers find molecular player involved with bladder inflammation

By Sathya Achia Abraham

A team of Virginia Commonwealth University School of Medicine researchers has identified a key role of a potential inflammatory mediator in bladder inflammation – or cystitis – findings that could one day be used to develop a treatment to help the more than 4 million Americans who suffer with the painful syndrome.

Advancing the understanding of the molecular make-up of this mediator is Liya Qiao, Ph.D., assistant professor in the VCU Department of Physiology and Biophysics, and her research team. They are examining the mechanical, physiological and biochemical functions of nerve growth factor, or NGF, in the urinary bladder during bladder inflammation.

In a study published in the February issue of the Journal of Biological Chemistry the team reported that NGF could be one of the major inflammatory mediators responsible for the bladder hypertrophy during bladder inflammation.

According to Qiao, NGF is produced by the damaged bladder lining, or urothelium, and acts on either the sensory nerve terminals or the bladder muscle cells in the bladder wall.

“The former regulates the sensitivity of the urinary bladder; the latter regulates the structure of the urinary bladder during cystitis,” she explained.

Further, she said that elevated NGF level in the inflamed bladder stimulates the bladder muscle cells to generate more collagen, which is then secreted out of the cells causing increases in the thickness of the bladder wall. 

“When we inject a specific NGF antibody to block the NGF action in a rat model of cystitis, the collagen production by the bladder muscle cells is decreased and the bladder hypertrophy caused by inflammation is reversed,” Qiao said. 

“Our findings that reduction of collagen up-regulation and bladder weight by NGF neutralizing antibody suggest that NGF analogs could also have potential therapeutic use for the treatment of cystitis-induced bladder abnormality,” she said.

NGF has already shown some promise through several clinical trials, including NGF gene therapy for the possible treatment of Alzheimer’s disease. According to Qiao, NGF antibody therapy is used in patients with osteoarthritis or with chronic lower back pain, representing a promising new therapeutic for the treatment of chronic pain.

Nobel Laureate Rita Levi-Montalcini first discovered NGF in the 1950s and isolated it from cancerous tissues that caused extremely rapid growth of nerve cells.

The urinary bladder is vulnerable to a variety of diseases and can become easily injured. For patients who undergo cyclophosphamide therapy for cancer treatment, constant irritation causes hemorrhagic cystitis, or inflammation of the bladder. An increase in bladder mass results and that causes urinary frequency, urgency and pain. This symptom is similar to that found in patients with interstitial cystitis, a painful bladder syndrome with unknown origin.

This work was supported in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.