Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome

Given the disputable link between nerve growth factor (NGF) and overactive bladder syndrome (OAB) and the lack of studies on its precursor (proNGF) in OAB, the aim of the study was to identify changes in the urinary levels of NGF and its proteolytic enzymes in aging women with OAB.

We examined the urinary proNGF/NGF ratio and its processing enzymes in aging women (50-80 years), comparing 20 controls and 20 subjects with OAB.

In contrast to previous reports correlating NGF to OAB symptoms, we found that proNGF/NGF ratio in the OAB group was twice as high compared to controls (p = 0.009) with a lower NGF levels in women with OAB without statistical significance [1.36 (Q1, Q3: 0.668, 2.39) vs. 1.7 (Q1, Q3: 1.27, 3.045) pg/mg creatinine in control group, p = 0.05]. Enzymatic activity of MMP-7, the main enzyme for extracellular proNGF maturation, was significantly increased in the OAB group and correlated positively with scores of OAB symptoms questionnaires. However, this was counteracted by several-folds increase in the MMP-9 enzyme responsible for NGF proteolysis. While these findings highlight the importance of changes in the proteolytic enzymes to maintain proNGF/NGF balance in OAB, analysis of covariates showed that these changes were attributed to age, insulin resistance and renal function.

NGF proteolysis imbalance can be clinically meaningful in OAB related to aging, rendering it as a potential therapeutic target. However, other age-related factors such as insulin resistance and renal function may contribute to the relationship between NGF and aging-related OAB phenotype.