title: Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways.
abstract: Stanniocalcin-1 (STC-1) protects against renal ischemia-reperfusion injury (RIRI). However, the molecular mechanisms remain widely unknown. STC-1 inhibits reactive oxygen species (ROS), whereas most ROS-mediated pathways are associated with ischemic injury. Therefore, to explore the mechanism, the effects of STC-1 on ROS-medicated pathways were studied. Non-traumatic vascular clamps were used to establish RIRI mouse models. The serum levels of STC-1, interleukin-6 (IL-6), interferon (IFN) γ, P53, and capase-3 were measured by ELISA kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by fluorescence spectrofluorometer. All these molecules changed significantly in a RIRI model mouse when compared with those in a sham control. Kidney cells were isolated from sham and model mice. STC-1 was overexpressed or knockout in these kidney cells. The molecules in ROS-medicated pathways were measured by real-time quantitative PCR and Western blot. The results showed that STC-1 is an effective ROS scavenger. The serum levels of STC-1, MDA and SOD activity were increased while the serum levels of IL-6, iIFN-γ, P53, and capase-3 were decreased in a model group when compared with a sham control (p < 0.05). Furthermore, the levels of STC-1,p53, phosphorylated mitogen-activated protein kinase kinase (p-MEKK-1), c-Jun N-terminal kinase (p-JNK), extracellular signal-regulated kinase (p-ERK), IkB kinase (p-IKK), nuclear factor (NF) κB, apoptosis signal-regulating kinase 1 (ASK-1) and caspase-3 changed significantly in kidney cells isolated from a RIRI model when compared to those isolated from a sham control (p < 0.05). Meanwhile, STC-1 overexpression or silence caused significant changes of the levels of these ROS-mediated molecules. Therefore, STC-1 maybe improve anti-inflammation, anti-oxidant and anti-apoptosis activities by affecting ROS-mediated pathways, especially the phospho-modifications of the respective proteins, resulting in the increase of SOD and reduce of capase-3, p53, IL-6 and IFN-γ.
authors.affiliation: Department of Nephrology, Shengjing Affiliated Hospital of China Medical University, Shenyang 110036, China. liudajun_sy2015@sina.com.
authors.forename: Dajun
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Shengjing Affiliated Hospital of China Medical University, Shenyang 110036, China. songxs1981@sina.com.
authors.forename: Huiping
authors.initials: H
authors.lastname: Shang
authors.affiliation: Department of Nephrology, Shengjing Affiliated Hospital of China Medical University, Shenyang 110036, China. yingliu1@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D015850:Interleukin-6; D016328:NF-kappa B; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D008315:Malondialdehyde; C051795:teleocalcin; D013482:Superoxide Dismutase; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D053148:Caspase 3
keywords: apoptosis signal-regulating kinase 1; caspase-3; extracellular signal-regulated kinase; p-IkB kinase; p-NF-κB; phosphorylated mitogen-activated protein kinase kinase; protein kinase C; reactive oxygen species-mediated pathways; renal ischemia-reperfusion injury; stanniocalcin-1