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.

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.

• Authors: M Zhu, L Wang, J Yang, K Xie, M Zhu, S Liu, C Xu, J Wang, L Gu, Z Ni, G Xu, M Che
• Journal: Transplantation proceedings (Transplant Proc) Vol. 51 Issue 3 Pg. 972-978 (Apr 2019) ISSN: 1873-2623 [Electronic] United States
• PMID: 30979490 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• STAT3 Transcription Factor
• Erythropoietin
• Janus Kinases

Topics

• Acute Lung Injury (drug therapy, metabolism, pathology)
• Animals
• Cell Line
• Cell Proliferation (drug effects)
• Endothelium, Vascular (metabolism, pathology)
• Erythropoietin (pharmacology)
• Humans
• Janus Kinases (metabolism)
• Kidney (blood supply)
• Kidney Diseases (drug therapy, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Reperfusion Injury (metabolism, pathology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)