Erythropoietin Ameliorates Lung Injury by Accelerating Pulmonary Endothelium Cell Proliferation via Janus Kinase-Signal Transducer and Activator of Transcription 3 Pathway After Kidney Ischemia and Reperfusion Injury

• Published in: Transplantation proceedings Vol. 51; no. 3; pp. 972 - 978
• Main Authors: Zhu, M., Wang, L., Yang, J., Xie, K., Liu, S., Xu, C., Wang, J., Gu, L., Ni, Z., Xu, G., Che, M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2019
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Animals; Cell Line; Cell Proliferation - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Erythropoietin - pharmacology; Humans; Janus Kinases - metabolism; Kidney - blood supply; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; Kidney Diseases - pathology; Male; Mice; Mice, Inbred C57BL; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2019.01.059

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. 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. 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. 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. •Erythropoietin remarkably attenuated pulmonary interstitial and alveolar epithelial edema.•The proliferation capacity of human umbilical vein endothelial cells was significantly increased under erythropoietin stimulation.•Erythropoietin is able to ameliorate acute lung tissue damage induced by renal ischemia and reperfusion and, at least in part, via the Jak-STAT3 pathway.