IC(Interstitial cystitis) is a significant chronic inflammatory disease of the bladder leading disastrous quality of life to patients. Although IC is considered as a chronic inflammatory condition of the bladder interstitium with unclear etiology,  there are evidences showing extraordinary inflammatory reactions are contributing disease progression of IC.
VEGF(vascular endothelial growth factor), a proinflammatory dimeric protein and a well-known endothelial permeability mediator which closely related to the pathopgenesis in obesity, autoimmune diseases, and cancers. NGF (nerve growth factor) is a neuropeptide contributing to target neural growth, maintenance, modulation of survival. 
This study aimed to investigate the expression of VEGF and NGF in classic ulcer type IC so that to analyze characteristic pathologic features which might provide some clues for effective prevention and management of IC.

It is an age and sex matched prospective study. Subjects are divided into three groups – classic ulcer type IC group (IC group), chronic bacterial cystitis group, and a control group which has no LUTS but harvested bladder tissue during other endoscopic surgery such as TURBt or urethral mass. Each group patients were 25 female patients with informed consent. After harvesting bladder tissue by endoscopic biopsy, expression of NGF and VEGF were analyzed using ELISA method. Statistical significance was analyzed using SPSS version 26 with Kruskal-Wallis test, p<0.05.

In bladder tissue of IC group, chronic inflammation, mucosal ulceration, and fibrosis were common findings. In cystitis group, chronic inflammation was found in some of the patients. Control group showed no specific findings. Expression of VEGF and NGF were significantly increased in IC and cystitis group compared with control group (p<0.05). Results are shown in figure 1 and 2. Although VEGF and NGF expression showed more increasing tendency in IC group than cystitis group, there were no statistical significance between two groups.

VEGF and NGF which are inflammatory reaction related modulators are increased in IC and chronic cystitis compared with control group. Increased expression of VEGF and NGF in IC compared with control group supports that clinical symptoms of IC are originated from pathologic changes of bladder tissue as a result of chronic inflammatory reactions.

Increased expression of VEGF and NGF in IC compared with control group suggesting anti-inflammatory treatment or anti-VEGF or anti-NGF treatment would provide preventive or protective benefit controlling clinical symptoms of IC.
 Similar findings were shown in chronic bacterial cystitis group although there was lower tendency compared with IC group. Considering significant portion of IC patients have clinical history of repeat symptomatic cystitis, there are suspected correlation between IC and chronic bacterial cystitis, taking in not independent line as a disease spectrum.

Saban R. Angiogenic factors, bladder neuroplasticity and interstitial cystitis—new pathobiological insights. Transl Androl Urol. 2015 ; 4(5): 555–562.
Saban R, Saban MR, Maier J, et al. Urothelial expression of neuropilins and VEGF receptors in control and interstitial cystitis patients. Am J Physiol Renal Physiol.  2008 ;295(6):F1613-23.
Tooke K, Girard B, Vizzard MA.  Functional effects of blocking VEGF/VEGFR2 signaling in the rat urinary bladder in acute and chronic CYP-induced cystitis. Am J Physiol Renal Physiol. 2019 ;317(7):F43-F51