Basic Research

• Nerve Growth Factor, Not PGE2, Is High in IC, OAB
  Liu HT, Tyagi P, Chancellor MB, Kuo HC. Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity. BJU Int. 2009 Sep 14. [Epub ahead of print]
  IC patients and some patients with overactive bladder (OAB) have high levels of nerve growth factor (NGF), but not prostaglandin E2 (PGE2), in their urine. The finding may have implications for both detection and treatment. Among experimental treatments that have been looked at are substances that inhibit NGF, thought to play a role in sensitivity or spasms, or medications that increase levels of PGE2-like activity, which may be low in IC. The researchers did not look at the effects of an NGF inhibitor or of extra PGE2, but they did look at levels of these substances in the urine of women with IC, women with OAB, and healthy women. The OAB group was divided into those who had overactivity of the bladder muscle (spasms) and those with simply with increased bladder sensation. NGF levels were high in the 40 women with IC and in 23 with detrusor overactivity but not in the 31 with increased bladder sensation or in the 27 healthy women. The women with IC had much higher levels of NGF than the women with detrusor overactivity. There were no differences among the groups in PGE2 levels.

• Receptor for New Molecule May Play Top Role in IC Inflammation
  Kutlu O, Akkaya E, Koksal IT, Bassorgun IC, Ciftcioglu MA, Sanlioglu S, Kukul E. Importance of TNF-related apoptosis-inducing ligand in pathogenesis of interstitial cystitis. Int Urol Nephrol. 2009 Aug 25. [Epub ahead of print]
  Turkish urologists have identified the cellular receptor in IC patients’ bladder tissue that may be the most important one in IC inflammation. They looked for different receptors for TNF-related apoptosis-inducing ligand or TRAIL. Staining IC bladder cells to reveal the receptors showed the receptor TRAIL-R4 to be the dominant one. Recently discovered, TRAIL plays a role in the death of abnormal cells and also in inflammation.

• Gene Expression Profiles Could Lead to Diagnostic Test
  Tseng LH, Chen I, Chen MY, Lee CL, Lo TS, Lloyd LK. Genome-based expression profiles as a single standardized microarray platform for the diagnosis of experimental interstitial cystitis: an array of 75 genes model. Int Urogynecol J Pelvic Floor Dysfunct. 2009 Jan 20. [Epub ahead of print] AND Tseng LH, Chen I, Chen MY, Lee CL, Lin YH, Lloyd LK. Genome-based expression profiles as a single standardized microarray platform for the diagnosis of bladder pain syndrome/interstitial cystitis: an array of 139 genes model. Int Urogynecol J Pelvic Floor Dysfunct. 2009 Feb 13. [Epub ahead of print]
  These researchers are studying the expression of various genes in IC bladder linings.  The genes that are highly expressed relate to the bladder lining and to the metabolism of glucose, lipids, nucleotides, chemicals foreign to the body, and amino acids.  In addition, the research implicated immune and inflammatory responses, various cell signaling pathways, and nerve function.  The team’s second study also pointed to mast cell activation and allergic inflammation.  The technique to study gene expression, using cDNA microarrays, may offer ways to diagnose IC/painful bladder syndrome (PBS) and discover drugs with potential as effective treatments, said the investigators.
  
  
• Nerve Type that Responds to “Hot Pepper” Pinpointed
  Malin SA, Christianson JA, Bielefeldt K, Davis BM. TPRV1 expression defines functionally distinct pelvic colon afferents. J Neurosci. 2009 Jan 21;29(3):743-52.
  The nerve receptor that responds to hot pepper-like substances is a focus of IC research because of its potential as a pain treatment target.  Called the vanilloid receptor or TRPV1, it is found on two distinct types of nerves that send signals from the colon back to the central nervous system, these researchers discovered.  One type fires fast, and the other, more slowly.  It’s the slow-firing nerves that respond to the hot pepper substance, capsaicin, and to two other irritators, mustard oil and acid.  The fast-firing type responds very little.  Because this receptor is thought to be responsible for inflammatory pain hypersensitivity in visceral organs, the unique role of these slow-firing nerves that have this receptor might be exploited to design treatments.
  
  
• IC Cats Have More Sensitive Bladder Coating
  Ikeda Y, Birder L, Buffington C, Roppolo J, Kanai A. Mucosal Muscarinic Receptors Enhance Bladder Activity in Cats With Feline Interstitial Cystitis. J Urol. 2009 Jan 19. [Epub ahead of print]
  Both calcium ions and muscarinic receptors (which overactive bladder drugs act on) can affect bladder contractions and spasms.  This team took a look at those two things in the bladders of cats with IC.  They identified alterations in calcium flow through the urothelium in cats with IC.  They also found that IC cat bladders were hypersensitive to a stimulator of the muscarinic receptor when the bladder coating (mucosal) layer was intact, but that sensitivity decreased markedly when the mucosal layer was gone, further corroboration that the bladder lining communicates with the rest of the bladder.
  
  
• Critical Step Discovered in APF Effects on Bladder Cells, Genes
  Planey SL, Keay SK, Zhang CO, Zacharias DA. Palmitoylation of Cytoskeletal Associated Protein 4 by DHHC2 Regulates Antiproliferative Factor-mediated Signaling. Mol Biol Cell. 2009 Jan 14. [Epub ahead of print]
  This basic research has discovered a critical step in how antiproliferative factor (APF) acts on bladder lining cells.  APF is the peptide discovered in IC patients’ urine that suppresses the proliferation of bladder lining cells.  The researchers had already learned that that APF binds strongly to the protein CKAP4, which plays a role in APF activity.  When the gene for CKAP4 is knocked down, APF signaling is stopped.  Now, the team has discovered that a process called palmitoylation of this protein, mediated by an enzyme known as DHHC2, is needed for APF to act.  Knocking down the gene for DHHC2 with a small interfering RNA inhibits the events that depend on APF and CKAP4.  Interfering RNAs, which help switch off genes, are being researched as a new approach to treating disease.
  
  
• New Ideas about Gene Expression Could Refocus IC Research
  Elgavish A. Epigenetic Reprogramming: A Possible Etiological Factor in Bladder Pain Syndrome/Interstitial Cystitis? J Urol. 2009 Jan 14. [Epub ahead of print]
  Basic research on the bladder lining, the nervous system, genetics, and processes that affect gene expression suggest that some reprogramming of gene expression (called epigenetic reprogramming) may explain the abnormalities in bladder lining cells, mast cells, and nerve cells seen in IC.  Particularly important may be the expression of genes that are important in maintaining adult stem cells.  These genes help silence the expression of other genes but inflammation may reverse that, leading to abnormalities in cell growth and maturation.  This idea is a new way of thinking that could refocus some research on the cause of IC and lead to new ways to diagnose and treat it, said the author.