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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Blotting, Western, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Fibronectins, Immunohistochemistry, Janus Kinase 2, Kidney Glomerulus, Male, Microscopy, Electron, Transmission, Peroxynitrous Acid, Phosphorylation, RNA, Messenger, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, STAT1 Transcription Factor, STAT3 Transcription Factor, Signal Transduction, Transforming Growth Factor beta, Tyrosine, Uric Acid.
user
Does peroxynitrite mediate glomerular lesion of diabetic rat via JAK/STAT signaling pathway? Context: Peroxynitrite, a highly reactive oxidant produced by the reaction of nitric oxide with free radicals superoxide, has been indicated to be involved in many diseases. However, the contributions of peroxynitrite to diabetic nephropathy and the underlying mechanism have not been fully explored. The present study was designed to evaluate the role and the underlying mechanism of peroxynitrite in glomerular lesion of diabetic rat. Diabetes was induced in male Wistar rats by i.p. injection of streptozotocin, and urate was used as a specific scavenger of peroxynitrite; the pathological changes of rat glomerulus were evaluated by hematoxylin and eosin, periodic acid-Schiff staining and transmission electron microscopy observation; immunohistochemistry and Western blot were used to detect the content of nitrotyrosine (the marker of peroxynitrite) in renal cortex; the expression levels of tyrosine phosphorylation of JAK2, STAT1, and STAT3 were assessed by Western blot assay; RT-PCR and Western blot were used to assay expression levels of transforming growth factor (TGF)-beta1 and fibronectin; biochemical indicators of renal function were also detected. The content of nitrotyrosine was increased, consistent with the pathological changes of glomerulus and renal dysfunction in the diabetes group. Urate prevented the formation of nitrotyrosine in rat glomerulus and attenuated the pathological alterations. Furthermore, urate inhibited the activation of JAK2, STAT1, and STAT3. Finally, homogenates from renal cortices demonstrated reduced expression of TGF- beta1 and fibronectin under urate treatment.
assistant
Our findings thus provides in vivo evidence that exaggerated peroxynitrite formation mediates the glomerular lesion in, at least, Type 1 diabetes, which may function through JAK/STAT signaling pathway. Final Decision: yes