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

Abstract

Introduction and hypothesis The aim of the study was to investigate the molecular signatures underlying bladder pain syndrome/interstitial cystitis (BPS/IC) using cDNA microarray. Methods Microarray gene expression profiles were studied in a matched case-control study by using a system of conditional regression modeling. ResultsThe main findings are summarized as follows: Firstly, a "139-gene" model was discovered to contain high expressions of bladder epithelium, which feature in BPS/IC. Secondly, complex metabolic reactions, including carbohydrate, lipid, cofactors, vitamins, xenobiotics, nucleotide, and amino acid metabolisms, were found to have a strong relationship with bladder smooth muscle contraction through IC status. Thirdly, we found the transcriptional regulations of IC-induced bladder smooth muscle contraction status, including the level of contractile force, tissue homeostasis, energy homeostasis, and the development of the nervous system. In addition, our study suggested the mast-cell activation mediated by the high-affinity receptor of Fc epsilon RI triggering allergic inflammation through IC status. Such genetic changes, jointly termed "bladder remodeling," can constitute an important long-term consequence of BPS/IC. Conclusions The success of this innovation has supported the use of microarray-based expression profiling as a single standardized platform for diagnosis of BPS/IC and offers drug discovery.The abstract of this article contained some errors that were overlooked or introduced while the manuscript was being prepared for publication. The corrected abstract is reproduced here.

A genome‐scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome

“…Exploratory pathway analysis showed multiple sites in the MAPK pathway that exhibited decreased methylation in participants with IC/BPS compared to controls and a few genes in this pathway have more than one differentially methylated CpG site. Although the mechanistic relationship between the MAPK signaling pathway and the pathophysiology of IC/BPS remains to be defined, increased gene expression in this pathway has been reported in previous studies . In general, p38 MAP kinase is associated with inhibition of cell growth, inflammation, and with mediating apoptosis in different cell types.…”

“…Multiple studies have investigated differential expression of genes in the urine sediment and bladder biopsies from patients with IC/BPS . Sensory, inflammatory, and apoptotic pathways have all been suggested to play a role in this heterogeneous condition.…”

Intravesical liposome therapy for interstitial cystitis

“…Nuclear receptor superfamily PPAR are considered to play an important role in the anti‐inflammatory effect of sphingomyelin. PPAR are endogenously controlled molecular switches for sensing the intracellular nutrient concentrations, and for regulating the gene expression in maintenance of both metabolic and immune homeostasis . PPAR‐γ is ubiquitously expressed in the urothelium and CD4 + T cells, where its activation is likely to attenuate the inflammatory responses through reduced adipocytokine signaling .…”

“…Based on studies involving wild‐type and PPAR‐γ knockout mice, the anti‐inflammatory effect of sphingomyelin is enhanced by PPAR‐γ expressed in the epithelial and immune cells . The patterns of genes upregulated by sphingomyelin are chemokines and chemokine receptors expressed in epithelial cells, and those involved in cell trafficking ( Ccl19 , Ccl11 , Ccl20 , Cxcl9 , Cxcl11 ), genes involved in CD4 + T cell differentiation and fate, including Th1 (interferon‐γ), Th17 (IL‐17 and IL‐23), Th2 (IL‐4, IL‐13, IL‐13R) and Treg (IL‐10R).…”