Interstitial Cystitis (IC), also known as painful bladder syndrome (PBS), is a chronic disease that significantly reduces the quality of life for patients [1]. Current experimentation studying biopsies of bladder epithelial cells from patients with IC reveals that changes in these bladder cells’ expression may be associated with the disease [1]. The changes in expression antiproliferative factor, interleukin-2, 4, 6, 8, tumor necrosis factor, nerve growth factor, insulin growth factor, transforming growth factor alpha, etc. may be attributed to the cause of this disease. Still, the etiology of IC is currently not fully understood and there are currently no uniformly established treatment strategies. However, hypotheses include sustained neurogenic inflammation, absorption of toxic substances, a deficient mucus layer or a leaky urothelium as potential causes for chronic inflammation. For this reason, selenoproteins might have a role in regulating this inflammation. Selenoproteins are a class of proteins containing one or multiple selenocysteine residues and have a unique translation process [2]. They play a significant role in inflammatory responses within the body and even include therapeutic remedies for cancer and induced oxidative damage [2]. Selenium deficiency is known to cause a weakened immune system and negatively impacts immune cells during activation and proliferation. This project aims to identify the correlation between inflammatory response genes, including those of selenoproteins, and Interstitial Cystitis through a comparative analysis of gene expression in IC and non-IC patients.

Using a gene expression profile from previous study done on ulcerative cystitis, we analyzed twenty different selenoproteins and their possible involvement in the inflammatory response associated with IC [3]. As a control, known chemical markers of IC (including interleukins and anti-proliferative factors) was also analyzed. Finally, we determined the highly upregulated and downregulated genes to explore novel pathways that might be involved in IC development. The final goal of this project is to create a searchable database that provides information about expression values of genes in patients with Interstitial Cystitis. This database contains the names of over 50,000 genes, their accession numbers, and their expression values. Raw data for each gene is generated as well as the average values for IC and control patients, and the ratio between these two numbers.

Of the genes studied, tRNAU1AP, VIMP, SEPSECS, SEPHS1, GPX2 and GPX4 had significant changes in gene expression level, with increases in tRNAU1AP, SEPSECS, SEPH1 and decreases in GPX2 and GPX4. Taking genes known to exhibit significant changes as a control, the selenoproteins listed all had ratios significantly below 1 or below 1, demonstrating that these genes are important biochemical markers in patients with IC, which gives insight into inflammatory pathways that result in the disease. Control gene marks like CXCL6 and IL3RA were highly expressed in IC patients and VEGFB and EGFR were downregulated. Interestingly, the SERPINA1 gene, with known associations with pulmonary disease, and BCL2A, which is upregulated by extracellular factors, were the two most highly expressed genes in the patients.

An analysis of a gene expression profile reveals that when compared to control and healthy patients, patients with IC have a higher expression of immune system response, cell communication and inflammatory response genes. We also determined that selenoproteins do have a significant role in the inflammatory and immune responses to IC.

The implications of this analysis is that since certain selenoproteins have a notable role in these pathways, they could be used in IC therapy and treatments.

Cho, Y.S., Interstitial Cystitis/Bladder Pain Syndrome: A Urologic Mystery. International neurourology journal, 2016. 20(1): p. 3-4.
Hariharan, S. and S. Dharmaraj, Selenium and selenoproteins: it's role in regulation of inflammation. Inflammopharmacology, 2020. 28(3): p. 667-695.
Gamper, M., et al., Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis. BMC Genomics, 2009. 10: p. 199.