Expression of mechano-growth factor (MGF) in refractory overactive bladder

Abstract

Overactive bladder (OAB) is a urological symptom complex defined by urinary urgency. It can have a devastating impact on an individual’s quality of life and leads to significant financial cost. Insulin-like growth factor 1 (IGF-1) is a protein hormone involved in a broad range of processes including cell proliferation and differentiation. IGF-1 is also regulated through alternative splicing. While the primaryIGF-1Eatranscript is highly expressed in liver, the alternativeIGF-1Ectranscript encodes the proteolytically-derived MGF peptide and has been primarily studied in skeletal muscle. MGF has been shown to stimulate satellite cell proliferation following tissue mechanical stretch or injury, but the role of MGF in smooth muscle, such as the detrusor muscle of the bladder, has been little explored. The aim of this study was to explore the expression of MGF in bladder biopsies from patients with OAB and age-matched controls.We show using immunohistochemistry that MGF is widely expressed in bladder tissue. Quantification of MGF expression by western blot showed that average MGF expression is more than doubled in OAB biopsies compared to controls (mean MGF in OAB=0.51±0.1, n=23; mean MGF in controls=0.22±0.07, n=9; p=0.05). Furthermore, there is an inverse correlation between MGF protein levels and symptom severity, as determined by the urodynamic parameter maximum cystometric capacity (correlation=0.53, p=0.03 n=16). MGF expression was highest in OAB biopsies with strong expression of the muscle cell markerDES. Combined with our observation that MGF induces cell proliferation in primary bladder cultures, our data suggests that high MGF expression in OAB patients may represent an attempted protective response in the bladder.