Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome
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ORIGINAL ARTICLE
Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome Abubakr H. Mossa1 · Philippe G. Cammisotto1 · Samer Shamout1,2 · Lysanne Campeau1,2 Received: 21 June 2020 / Accepted: 21 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose 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. Methods 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. Results 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. Conclusion 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. Keywords Nerve growth factor · Aging female · Overactive bladder · proNGF · MMP-7 · MMP-9 Abbreviations HOMA-I Homeostatic model assessment of insulin resistance GFR Glomerular filtration rate MPP-7 Matrix metalloproteinase-7 MPP-9 Matrix metalloproteinase-9 PGE2 Prostaglandin E2 NO Nitric oxide Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00345-020-03422-6) contains supplementary material, which is available to authorized users. * Lysanne Campeau [email protected] 1
Lady Davis Research Institute, McGill University, 3755, Chemin de la cote‑Ste‑Catherine, Montreal, QC H3T 1E2, Canada
Urology Department, Jewish General Hospital, Montreal, QC, Canada
2
NGF Nerve growth factor proNGF Precursor of nerve growth factor OAB Overactive bladder TIMP-1 Tissue inhibitor of mettaloproteinases-1 P75NTR P75 neurotrophin receptor TrkA Tropomyosin receptor kinase
Introduction OAB is defined as voiding urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia [1]. OAB disturbs the quali
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