Erythropoietin protects against rhabdomyolysis-induced acute kidney injury by modulating macrophage polarization.

Abstract

Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms. EPO was found to ameliorate kidney injuries by reducing macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. It was also confirmed that EPO could directly suppress pro-inflammatory responses of M1 macrophages and promote M2 marker expression in vitro. Data indicated the possible involvement of Jak2/STAT3/STAT6 pathway in the augmentation of EPO on M2 polarization. These results improved the understanding of the immunoregulatory capacity of EPO on macrophages, which might optimize the therapeutic modalities of EPO.

• Authors: Shuo Wang, Chao Zhang, Jiawei Li, Sidikejiang Niyazi, Long Zheng, Ming Xu, Ruiming Rong, Cheng Yang, Tongyu Zhu
• Journal: Cell death & disease (Cell Death Dis) Vol. 8 Issue 4 Pg. e2725 (04 06 2017) ISSN: 2041-4889 [Electronic] England
• PMID: 28383559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• STAT3 Transcription Factor
• STAT6 Transcription Factor
• Stat3 protein, mouse
• Stat6 protein, mouse
• Erythropoietin
• Jak2 protein, mouse
• Janus Kinase 2

Topics

• Acute Kidney Injury (drug therapy, etiology, immunology)
• Animals
• Erythropoietin (pharmacology)
• Janus Kinase 2 (immunology)
• Macrophages (immunology, pathology)
• Mice
• Rhabdomyolysis (complications, immunology, pathology)
• STAT3 Transcription Factor (immunology)
• STAT6 Transcription Factor (immunology)
• Signal Transduction (drug effects, immunology)