Benign prostatic hyperplasia often causes intravesical obstruction in elderly men; however, the processes of aging and bladder outlet obstruction independently evoke alterations in the structure and function of the bladder. These changes lead to lower urinary tract symptoms; however, it is difficult to separate the effects of prostatic obstruction on the bladder from those of aging. Nevertheless, few studies have focused on elucidating the pathophysiological mechanisms in the aged bladder. Bladder dysfunction due to detrusor instability (caused by old age) is considered to be associated with chronic ischaemia and inflammation. The aim of this study was to explore the role of tumour necrosis factor (TNF)-like ligand 1A (TL1A) and death-domain receptor (DR)3 in the ischaemic and inflammatory process of aged bladder dysfunction. Sixteen bladder tissue samples collected from patients with urothelial tumours of the bladder were divided into two groups according to age: group 1 (controls, n=8) and group 2 (aged group, n=8). Urodynamic examinations were preformed before radical cystectomy. The full-thickness bladder tissues were obtained at least 5 cm away from the margin of the tumours. The mRNA expression levels of TL1A, DR3, von Willebrand factor (vWF), interleukin (IL)-6 and nerve growth factor (NGF) in the two groups were determined using real-time reverse transcription-PCR and the protein expression levels of TL1A, DR3 and p65 were determined by western blot analysis. The TL1A and DR3 mRNA and protein expression levels of the aged bladders were upregulated compared to the control group (p<0.05). Compared to the control, the mRNA expression levels of vWF in the aged bladder tissues were markedly lower (p<0.01); however, the mRNA expression levels of IL-6 were significantly higher in the aged bladder tissues (p<0.01) compared to the control. No significant difference in NGF mRNA expression between the two groups was detected (p>0.05). In conclusion, the aged bladder was associated with ischaemic and inflammatory alterations in comparison to the control group. TL1A and DR3 may play an important role in the pathophysiological process of the aged bladder.
Keywords: tumour necrosis factor-like ligand 1A; vascular endothelial cell growth inhibitor; death-domain receptor 3; bladder ischaemia; lower urinary tract symptoms; aging bladder.