Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase

Wang, Rui; Yin, Jianyong; Lu, Zeyuan; Zhang, Guangyuan; Li, Junhui; Xing, Tao; Zhuang, Songlin; Wang, Niansong

doi:10.1016/j.ebiom.2016.05.017

Cited by 51 publications

(56 citation statements)

References 49 publications

(67 reference statements)

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“…Cumulative evidence has suggested that contrast agent leads to renal tubular cell apoptosis through the ROS pathway, the stress kinase pathway and the intrinsic apoptotic pathway [40,41]. Our study proved that caspase3 activation, in other words, the intrinsic apoptotic pathway was involved in the contrast induced renal injury, which was reported in our recent studies [24,25,39] and other reports [38]. Sulodexide might exert its inhibitory effect on apoptosis via a direct inhibition of caspases, which was evidenced that Sulodexide increased the viability of H 2 O 2 -injured HK2 cells in vitro, or in an indirect manner by its ability of ROS clearance.…”

Section: Discussionsupporting

confidence: 70%

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Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Zhao

Yin

et al. 2016

Cell Physiol Biochem

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Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H₂O₂-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

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Section: Discussionsupporting

confidence: 70%

“…CIN model was established as we described previously [24,25]. Briefly, rats were given a tail vein injection of indomethacin (5mg/kg), followed by Ioversol (3g/kg organically bound iodine) and L-NAME (10 mg/kg).…”

Section: Animal Experimental Protocols and Rat Cin Modelmentioning

confidence: 99%

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Zhao

Yin

et al. 2016

Cell Physiol Biochem

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“…It has been reported that during the renal IRI, oxidative stress is one of the most critical mechanisms involved in the tubular cellular damage and apoptosis [26, 27]. Our previous studies found that MDA was increased while SOD was increased in rat AKI models [28–30]. Consistently, the present study demonstrated that the improvement of renal function in IRI rats by sulodexide was accompanied with decreased oxidative stress levels.…”

Section: Discussionsupporting

confidence: 90%

Sulodexide pretreatment attenuates renal ischemia-reperfusion injury in rats

Yin

Chen

et al. 2016

Oncotarget

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Sulodexide is a potent antithrombin agent, however, whether it has beneficial effects on renal ischemia-reperfusion injury (IRI) remains unknown. In the present study, we assessed the therapeutic effects of sulodexide in renal IRI and tried to investigate the potential mechanism. One dose of sulodexide was injected intravenously in Sprague-Dawley rats 30 min before bilateral kidney ischemia for 45 min. The animals were sacrificed at 3h and 24h respectively. Our results showed that sulodexide pretreatment improved renal dysfunction and alleviated tubular pathological injury at 24h after reperfusion, which was accompanied with inhibition of oxidative stress, inflammation and cell apoptosis. Moreover, we noticed that antithrombin III (ATIII) was activated at 3h after reperfusion, which preceded the alleviation of renal injury. For in vitro study, hypoxia/reoxygenation (H/R) injury model for HK2 cells was carried out and apoptosis and reactive oxygen species (ROS) levels were evaluated after sulodexide pretreatment. Consistently, sulodexide pretreatment could reduce apoptosis and ROS level in HK2 cells under H/R injury. Taken together, sulodexide pretreatment might attenuate renal IRI through inhibition of inflammation, oxidative stress and apoptosis, and activation of ATIII.

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“…Under hypoxia, HIF-1α regulates the expression of target genes by binding to the core sequence at the promoter region of the target genes (18). For example, it was reported that renalase, an amine oxidase secreted by the proximal tubule, was upregulated by hypoxia via a HIF-1α-dependent mechanism (19,20). HIF-1α is closely associated with the invasion, metastasis and prognosis of tumors (21).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-inducible factor 1α participates in hypoxia-induced epithelial-mesenchymal transition via response gene to complement 32

Zhu

Zhao

2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to explore the function of response gene to complement 32 (RGC-32) in hypoxia-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer. Three kinds of hypoxia-inducible factor 1α (HIF-1α) small interfering (si)RNA were synthesized and the different effects on the expression of HIF-1α were detected by western blotting. In human pancreatic cancer BxPC-3 cells, HIF-1α levels were diminished using siRNA transfection or HIF-1α inhibitor pretreatment, and the expression levels of RGC-32 and EMT-associated proteins were analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. Subsequently, the protein levels of epithelial marker, E-cadherin, and mesenchymal marker, vimentin, were determined by western blotting. Results demonstrated that HIF-1α-Homo-488 siRNA and HIF-1α-Homo-1216 siRNA diminished the protein level of HIF-1α. Compared with normoxia, hypoxia induced the levels of HIF-1α, RGC-32, N-cadherin and vimentin, but suppressed the expression of E-cadherin and cytokeratins. The inhibition of HIF-1α by HIF-1α-Homo-1216 siRNA transfection or HIF-1α inhibitor repressed hypoxia-induced HIF-1α, RGC-32, N-cadherin and vimentin, but increased the expression of E-cadherin and cytokeratins. When RGC-32 was knocked down, hypoxia-induced vimentin was suppressed; however, hypoxia-suppressed N-cadherin was released. In conclusion, the present results demonstrated that hypoxia induced the expression of HIF-1α to activate the levels of RGC-32, in turn to regulate the expression EMT-associated proteins for EMT. These findings revealed the function of RGC-32 in hypoxia-induced EMT and may have identified a novel link between HIF-1α and EMT for pancreatic cancer therapy. IntroductionPancreatic cancer is a highly lethal human gastrointestinal cancer (1). Although increasing methods are being applied for pancreatic cancer treatment, such as surgical resection and radiotherapy, the 5-year relative survival rate remains very dismal. A potential reason for the failure of the classical therapeutic approach may be explained by its high metastatic potential (2). Thus, it is critical to reveal the metastasis mechanism of pancreatic cancer. Epithelial-mesenchymal transition (EMT), the conversion from an epithelial to a mesenchymal phenotype, is a vital process for cancer invasion to surrounding tissues or metastasis to other organs (3). During the process of EMT, typical morphological changes occur, such as cell invasion and motility (4). The molecular indicators for EMT are the decrease of epithelial markers, such as E-cadherin, and the increase in the levels of mesenchymal markers, such as N-cadherin and vimentin (5). Significant efforts are required to investigate the mechanism of EMT for cancer control and the improvement of cure rate.Response gene to complement 32 (RGC-32), first identified in 1998, is induced by complement and involved in cell cycle activation (6). RGC-32 is comprehensively expressed in the placenta, skeletal muscle, kidney, ...

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Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase

Cited by 51 publications

References 49 publications

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Sulodexide pretreatment attenuates renal ischemia-reperfusion injury in rats

Hypoxia-inducible factor 1α participates in hypoxia-induced epithelial-mesenchymal transition via response gene to complement 32

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