ABSTRACT
Interstitial cystitis (IC) is a heterogeneous syndrome with unknown etiology, and microRNAs (miRs) were found to be involved in IC. In our study, we aim to explore the role of miR-132 in the inflammatory response and detrusor fibrosis in IC through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway in rat models. A rat model of IC was established and treated with the miR-132 mimic, miR-132 inhibitor, and/or JAK-STAT signaling pathway inhibitor AG490. Enzyme-linked immunosorbent assay was applied to measure the expression of interleukin (IL)-6, IL-10, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1). The urodynamic test was performed to assess urodynamic parameters, and reverse transcription quantitative polymerase chain reaction and Western blot analysis for the expression of miR-132, STAT4, suppressors of cytokine signaling 3 (SOCS3), JAK2, vascular endothelial growth factor (VEGF), IFN-γ, and TNF-α. IC rats treated with miR-132 inhibitor and AG490 had decreased collagen fiber, inflammatory cell infiltration, and mast cells, lower expression of IL-6, IL-10, IFN-γ, TNF-α, ICAM-1, collagens I and III, and alleviated urodynamic parameters and decreased expression of STAT4, VEGF, JAK2, IFN-γ, TNF-α, and increased expression of SOCS3. Taken together, our data indicate that downregulation of miR-132 alleviates inflammatory response and detrusor fibrosis in IC via the inhibition of the JAK-STAT signaling pathway.
Subject(s)
Cystitis, Interstitial/metabolism , Inflammation/metabolism , Janus Kinases/metabolism , MicroRNAs/metabolism , Animals , Cystitis, Interstitial/drug therapy , Female , Humans , Immunohistochemistry , In Vitro Techniques , Inflammation/drug therapy , Janus Kinase 2/metabolism , MicroRNAs/genetics , Rats , Rats, Sprague-Dawley , STAT4 Transcription Factor/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Tumor Necrosis Factor-alpha/metabolism , Tyrphostins/therapeutic use , Vascular Endothelial Growth Factor A/metabolismABSTRACT
OBJECTIVE: The purpose of this study was to investigate the value of integrated backscatter (IBS) of kidneys in acute organophosphorus compound poisoning in rabbits. METHODS: Eighteen rabbits were poisoned by dimethyl dichlorovinyl phosphate to establish animal models. Sonographic examinations were performed before (T0) and after (T1-T9) the rabbits were poisoned. The echo and size of kidneys were evaluated by 2-dimensional gray scale sonography. Changes of the renal cortex and medulla were analyzed quantitatively with IBS. RESULTS: No change of the cortex echo was found before and after poisoning. A significant change of the volume of kidneys on both sides began at T6 compared with that at T0 (P < .05). A significant change of renal length on both sides began at T7 compared with that at T0 (P < .05). The volume change was earlier than that of length. A significant change in IBS% of the renal cortex began at T5 compared with that at T0 (P < .05), whereas a significant change in IBS% of the renal medulla began at T6 compared with that at T(0) (P < .05). The change in IBS% of the renal cortex was earlier. CONCLUSIONS: More useful information provided by IBS% has been found in acute organophosphorus compound poisoning in rabbits.
