Urinary Metabolomic and Proteomic Analyses of a Prostatic Inflammation Mouse Model
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ABSTRACT: Lower urinary tract symptoms (LUTS) relate to storage and/or voiding disturbances which are common among aging men. Disease etiology is largely unknown, and diagnosis is currently based on subjective symptom scores. While mainstay treatments can be ineffective and bothersome, biomarker discovery efforts may facilitate objective diagnostic criteria for personalized medicine and new potential druggable pathways. Since inflammation is one of its plausible etiologies, the goal of this project is to explore urinary metabolite and protein biomarkers as a non-invasive method to diagnose of LUTS which is induced by inflammation. Herein, a bacterial-induced prostatic inflammation model was established with C57BL/6J mice infected with uropathogenic E. coli 1677. Mouse urine samples were collected from control and treatment mice. Mass Spectrometry-based multi-omics analysis was employed here to discover urinary protein and metabolite-based biomarkers specific to prostatic inflammation-induced LUTS. We investigated the use of isobaric dimethylated leucine (DiLeu) labeling for metabolite identification and quantification for the mouse urine samples, and because of the use of DiLeu labeling, we combined metabolomics and proteomics on the same LC-MS platform. Overall, a total of 143 amine-containing metabolites and 1058 urinary proteins were identified and quantified, among them, 14 metabolites and 168 proteins were significantly changed by the inflammation treatment. Five metabolic pathways and four inflammatory-related biological processes were potentially disrupted. After compare with LUTS patient and other previously report, metabolite creatine and protein Polymeric Ig receptor presents especially attractive combined biomarker for prostatic inflammation induced LUTS and could be further used as the LUTS patient stratification. Overall, this study found urine metabolomics and proteomics to be an informative and noninvasive method for candidate biomarkers determination and etiologies classification of LUTS induced by inflammation.
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Urine
SUBMITTER: Pingli Wei
LAB HEAD: Lingjun Li
PROVIDER: PXD018023 | Pride | 2021-05-03
REPOSITORIES: Pride
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