Erythropoietin Attenuates Experimental Contrast-Induced Nephrology: A Role for the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling Pathway

Abstract

The aim of the present study was to investigate the effect of erythropoietin (EPO) on contrast-induced nephrology (CIN) in vivo and in vitro. Male C57BL/6J mice were divided into four groups: control, CIN (iohexol 6.0 g/kg), EPO (3,000 IU/kg), and CIN+EPO. Hematoxylin and eosin (H&E) staining and biochemical index analyses were performed to evaluate renal injury. The cellular proliferation rate was detected using the Cell Counting Kit-8 (CCK-8) assay. In addition, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometric assay were used to assess the apoptosis of tissue and cells, respectively. Renal protein expression associated with apoptosis, pyroptosis, and signaling pathways was determined by Western blot (WB) assays for tissues and cells. The results showed that EPO significantly decreased serum creatinine, blood urea nitrogen, and cystatin C levels and alleviated renal histological changes in vivo. The protein levels of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway components were overexpressed in the EPO treatment group. Furthermore, EPO suppressed the cell apoptosis and pyroptosis; decreased the protein levels of cleaved caspase-3, Bax, gasdermin D (GSDMD), and caspase-1; and enhanced the expression of Bcl-2. In summary, EPO could exert renoprotective effect by activating the JAK2/STAT3 signaling pathway, which may be a novel potential therapy for the treatment of CIN in the clinic.

Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma

“…CTSV, a lysosomal cysteine protease, is expressed at increased levels in HCC and is an independent prognostic risk factor for HCC survival, and elevated CTSV expression is strongly correlated with an adverse prognosis in HCC ( Jing et al, 2018 ). EPO is a pleiotropic cytokine that regulates multiple cellular activities and attenuates pyroptosis ( Yang et al, 2021 ). EPO is increased in HCC and its production is inversely correlated with the overall prognosis of HCC ( Ke et al, 2017 ).…”

Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines

“…However, the activation of NF-κB and STAT3 takes place in dissimilar cytokines; while TNF potently activates the former, IL-6 strongly activates STAT3. A previous study also demonstrated the potential ability of erythropoietin to activate NF-κB by activating JAK2 kinase [ 48 ]. Therefore, the inhibition of JAK2 kinase activation could be pivotal to suppressing STAT3 activation.…”

Erythropoietin mitigated thioacetamide-induced renal injury via JAK2/STAT5 and AMPK pathway

“…Both families have been confirmed in mammals. Animals AKI or ischemia–reperfusion (I/R) damage models have demonstrated the involvement of JAK 1 and 2 as well as STAT 3, 5, and 6 in the development of AKI 13 . It is generally recognized that many cytokines, including TNF-α and IL-6, have a role in the immune response via the JAK/STAT pathway 14 .…”