M Zhu5, L Wang2, J Yang3, K Xie4, M Zhu5, S Liu5, C Xu4, J Wang1, L Gu4, Z Ni4, G Xu6, M Che7. 1. Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 2. Department of Emergency, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 4. Department of Nephrology, Molecular Cell Lab for Kidney Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 5. Department of Nephrology, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 6. Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: xugenxing@medmail.com.cn. 7. Department of Nephrology, Molecular Cell Lab for Kidney Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: cather1983@126.com.
Abstract
BACKGROUND/AIMS: Kidney ischemia and reperfusion injury could cause microvascular barrier dysfunction, lung inflammatory cascades activation, and programmed cell death of pulmonary endothelium, leading to acute lung injury. Our study aimed at determining whether erythropoietin (EPO) can ameliorate lung dysfunction following renal ischemia and reperfusion (IR) injury and explored the underlying mechanisms. METHODS: In vivo, C57BL/6 mice received EPO (6000 U/kg) before right renal vascular pedicles clamping for 30 minutes, followed by 24 hours of reperfusion. The lung histopathologic changes and inflammatory cytokines expression were assessed. In vitro, cultured human umbilical vein endothelial cells were treated with EPO, and apoptosis rate, proliferation capacity, and phosphorylation status of the Janus kinase-signal transducer and activator of transcription 3 (Jak-STAT3) pathway were measured respectively in the presence or absence of lipopolysaccharide stimulation. RESULTS: In vivo, EPO remarkably attenuated pulmonary interstitial and alveolar epithelial edema caused by renal IR injury. In vitro, the proliferation capacity of human umbilical vein endothelial cells was significantly increased under EPO stimulation, which correlated with changes in Jak-STAT3 signaling. CONCLUSION: Our data indicated that EPO is able to ameliorate acute lung tissue damage induced by renal IR, and at least in part, via the Jak-STAT3 pathway.
BACKGROUND/AIMS: Kidney ischemia and reperfusion injury could cause microvascular barrier dysfunction, lung inflammatory cascades activation, and programmed cell death of pulmonary endothelium, leading to acute lung injury. Our study aimed at determining whether erythropoietin (EPO) can ameliorate lung dysfunction following renal ischemia and reperfusion (IR) injury and explored the underlying mechanisms. METHODS: In vivo, C57BL/6 mice received EPO (6000 U/kg) before right renal vascular pedicles clamping for 30 minutes, followed by 24 hours of reperfusion. The lung histopathologic changes and inflammatory cytokines expression were assessed. In vitro, cultured human umbilical vein endothelial cells were treated with EPO, and apoptosis rate, proliferation capacity, and phosphorylation status of the Janus kinase-signal transducer and activator of transcription 3 (Jak-STAT3) pathway were measured respectively in the presence or absence of lipopolysaccharide stimulation. RESULTS: In vivo, EPO remarkably attenuated pulmonary interstitial and alveolar epithelial edema caused by renal IR injury. In vitro, the proliferation capacity of human umbilical vein endothelial cells was significantly increased under EPO stimulation, which correlated with changes in Jak-STAT3 signaling. CONCLUSION: Our data indicated that EPO is able to ameliorate acute lung tissue damage induced by renal IR, and at least in part, via the Jak-STAT3 pathway.
Authors: Walaa H El-Maadawy; Marwa Hassan; Ehab Hafiz; Mohamed H Badawy; Samir Eldahshan; AbdulRahman AbuSeada; Maha A M El-Shazly; Mosad A Ghareeb Journal: Sci Rep Date: 2022-04-14 Impact factor: 4.996
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