Increased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor associated with glomerulation formation in patients with interstitial cystitis

Abstract

Objective: To examine whether hypoxia occurs in the bladders of patients with interstitial cystitis (IC) by monitoring the expression of hypoxia-inducible factor-1 (HIF-1) and VEGF. Previous studies have reported that bladder perfusion is decreased in patients with IC. Hypoxia induces overexpression of vascular endothelial growth factor (VEGF), which has been reported to be associated with the formation of glomerulations in patients with IC.

Methods: The study group consisted of 32 patients with IC, and the control group consisted of 8 volunteers. We obtained bladder biopsies from both groups and studied the expression of HIF-1α and VEGF proteins by immunoblotting and immunohistochemical and double immunofluorescent staining. Data were analyzed using the Mann-Whitney U test.

Results: Immunoblotting and immunostaining revealed that the expression of HIF-1α and VEGF proteins was increased in the study group compared with the control group. The relative intensities of HIF-1α and VEGF proteins were 60.60 ± 7.81 and 43.60 ± 5.37 in the study group and 26.20 ± 4.72 and 20.25 ± 1.45 in the control group, respectively. The overexpression of VEGF in study group biopsies was particularly evident in umbrella cells examined by confocal microscopy.

Conclusion: Our findings identified increased expression of HIF-1α in bladder tissue and overexpression of VEGF in umbrella cells from patients with IC. These events may be associated with glomerulation formation during hydrodistention in IC bladders. Thus, these molecular findings could offer the therapeutic mechanism for hyperbaric oxygenation application to patients with IC.