Project description:We compared the chnages in urinary bladder and iliac lymph nodes microRNAs in the control and experimental autoimmune cystitis in mice. A set of urinary bladder microRNAs (miRNAs) shows profound upregulation or downregulation in the expression profiles of the experimental IC as compared to control.
Project description:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating pain disorder of the bladder and urinary tract with poorly understood etiology. A definitive diagnosis of IC/BPS can be challenging because many symptoms of IC/BPS are shared with other urological disorders. An analysis of urine presents an attractive and non-invasive resource for monitoring and diagnosing IC/BPS. Here, a non-targeted LC-MS and LC-MS/MS-based peptidomics analysis of urine samples collected from IC/BPS patients were compared to urine samples from asymptomatic controls.
Project description:Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a clinical condition that manifests as a sensory hypersensitivity of unknown cause and is characterized by urinary frequency, bladder discomfort, and pelvic pain. In the present volatolomic study, we have analyzed the VOCs unique to urine specimens obtained from interstitial cystitis patients, in compassion to healthy controls.This is the novel finding from comprehensive and unbiased metabolomics analysis that urinary menthol is decreased in urine specimens from IC patients, and that the reduced menthol level in IC is potentially linked to the chronic inflammation, which is often observed in IC patients
Project description:Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette–Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a novel mouse anti-IFN-γ DNA aptamer and observed that intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed novel murine HIC mouse model with little migration into the blood. Our study provides the plausible basis for clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.
Project description:Antimicrobial peptides (AMPs) serve key proposed roles in defending the urinary tract against invading uropathogens, but individual AMPs bearing greatest responsibility for these functions remain largely unknown. We identified RegIIIγ as the most transcriptionally upregulated AMP in bladder transcriptomes following uropathogenic Escherichia coli (UPEC) infection. We confirmed induction of RegIIIγ mRNA during cystitis and pyelonephritis by quantitative RT-PCR. Immunoblotting demonstrates increased bladder and urinary RegIIIγ protein levels following UPEC infection. Immunostaining localizes RegIIIγ protein to urothelial cells of infected bladders and kidneys. Human patients with cystitis and pyelonephritis exhibit increased urine levels of the orthologous HIP/PAP protein. Recombinant RegIIIγ protein does not demonstrate bactericidal activity toward UPEC in vitro, but does kill Staphylococcus saprophyticus in a dose-dependent manner. RegIIIγ knockout and control urinary tracts contain comparable bacterial burden following experimental inoculation of UPEC as well as Gram-positive uropathogens. Thus, while RegIIIγ and HIP/PAP expression occurs in human and murine UTI, their specific functions in the urinary tract remain uncertain.
